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  Topic: Bioactive Secondary Metabolites In Nature, Sorry, this is long and a bit technical< Next Oldest | Next Newest >  
Louis



Posts: 6436
Joined: Jan. 2006

(Permalink) Posted: May 11 2007,14:49   

Hi All,

In response to a request by Arden and a topic "introduced" by FTK I thought I'd bung this up for shits and giggles!

It's taken from a very early version of my PhD thesis (i.e. prior to submission and examination, it was trimmed to shorten an already massive introduction and is quite rusty). I hope I can get the  images in and I am happy to elaborate on or explain any part of it.

This is a very very brief overview of a massive bit of chemistry/biochemistry that is only partially relevant to the goals of my PhD work, so if it's a bit waffley and non-technical remember it's come from the "setting the scene" section of my introduction as opposed to the real meat. I've also cut a few bits (mostly synthetic chem that isn't relevant) out so hopefully it makes some sort of coherent sense.

Cheers

Louis

1.General Introduction:

The importance of natural products in organic chemistry, and the scientific endeavour as a whole, cannot be overestimated. Natural products have formed both the backbone of, and the inspiration for, the pursuit of organic chemistry. Human societies have used chemicals derived from a wide variety of natural sources for an equally wide variety of purposes for millennia. From curare, a crude, dried extract of the plant Chrondrodendron tomentosum, prepared by sixteenth century South American Indians and used with lethal efficacy against the invading European colonists. To nutmeg, a humble spice derived from the ground kernel of the fruit from the tree Myristica fragrans, and widely used to obscure the taste of spoiled meat.1

It is however in the field of medicine where natural products have arguably made their greatest impact. Chemicals found in nature have been used as medicines by every human society throughout recorded history, there is even evidence that suggests that non-human primates self medicate with materials found in nature.2

Natural products and their chemistry don’t just have real world practical applications, profound scientific insights into the workings of nature have been derived from the study of natural products chemistry. Take for example the discovery of the effects of penicillin by Fleming in 1929, which aided in the development of modern medicine by demonstrating the potential use of certain chemicals (antibiotics) in fighting bacterial pathogens and was one of the founding discoveries in the germ theory of disease. 3 Perhaps most notable amongst classical discoveries though is the synthesis of urea by Wöhler in 1828, which helped to disprove the widely held belief in vitalism (i.e. that living matter and non-living matter were profoundly different). 4

The contribution made by natural products to medicine has not dwindled since the seminal works of the 19th and early 20th centuries, rather it has flourished. Many molecules isolated from nature are being used to grant us new insights into the workings of some of the most pernicious diseases to afflict humanity, and thus allow us to design treatments. This practice continues today, with some of the most important drugs such as Taxotere™ and Artemisinin being closely derived from natural products. In fact, roughly 61% of the 877 new chemical entities produced in the pharmaceutical industry world wide from 1981 to 2002 can be traced to natural products. 78% of antibacterials and 74% of anticancer compounds from that set of chemical entities are either natural products themselves or inspired by a natural product. 5

2.A Brief Comment About Secondary Metabolite Sources

Many species of microorganism produce structurally complex and highly biologically active secondary metabolites. For example the largest non-biopolymeric secondary metabolite isolated to date, maitotoxin (1), has been isolated from a single celled red tide dinoflagellate, Gambierdiscus toxicus.



Maitotoxin (1)

While the marine environment remains a very rich source of biologically active materials, the largest antibiotic producing microorganism genus discovered so far is a genus of actinomycete soil bacteria, Streptomyces. The number of antimicrobial compounds reported from the species of this genus per year increased almost exponentially for about two decades, followed by a steady rise to reach a peak in the 1970s, and with a substantial decline in the late 1980s and 1990s.6 This decline appears to be due to a fall off in screening efforts rather than an exhaustion of the potential of this genus. Recent re-screening of actinomycete derived antibiotics has produced some potentially useful antitumour compounds.

3. A Brief Overview of Secondary Metabolite Evolution

Any understanding of natural product biosynthesis must be tempered with some understanding of the origins of natural products and their import in nature. The existence of natural products immediately begs the question: why do these complex, cytotoxic chemical persist in nature? In other words, what does an organism gain by producing natural products? There are several hypotheses regarding the evolutionary significance and origins of natural products, and these have been extensively debated in the literature. 7-15

Most prominent among them are:

1. Natural products are essentially neutral with respect to selection pressure.

2. Natural products provide a reservoir of non-functional variety out of which new functional processes can emerge.

3. Natural products are waste or detoxification products derived from primary metabolism.

4. Natural products are a by-product of the enzymatic processes of primary and secondary metabolism, and it is the processes on which selection acts, as opposed to the natural products.

5. Natural products have had, at some time in the organism’s development, a functional metabolic role.

6. Natural products are a measure of the fitness of an organism. The ability to synthesise an array of natural products which may repel or attract other organisms has evolved as one facet of the organism’s survival strategy.

Whilst each proposal has some basis in the literature, the two proposals that are the most supported by the available data are proposal 6, and a modified version of proposal 2.

The initial problem with proposal 2 is that of teleology, in other words: pre-programmed purpose. Since evolution is not a purposeful process, this rather defeats this proposal.16 However, a re-examination of this proposal in terms of the “Screening Hypothesis” shows that it can be used as a rigourous explanation of the diversity and abundance of natural products.17 The Screening Hypothesis takes note of the fact that the property of molecular bioactivity is rare. It proposes that natural selection would favour organisms that can produce a wide diversity of chemical structures (a “screen”, by analogy to human efforts to create bioactive molecules) because these organisms would be more likely to make a “hit” bioactive molecule.

One of the most compelling pieces of evidence for this proposal is that the organisms that typically produce natural products are “simple” organisms that lack an immune system (with some notable exceptions like poison arrow frogs etc). Many of the antibodies produced by an organism’s immune system are currently redundant, they have evolved for antigens that they will never now encounter. This variety of antibodies is an essential facet of successful immune systems because diversity of antibodies at relatively cheap metabolic cost, allows an organism to safely encounter an equally wide variety of antigens. By analogy, diversity in natural product production provides a similar type of fitness for microorganisms.

However, proposal 2 relies heavily on the fact that the production of natural products is due to functional redundancy and high substrate tolerance in the enzymes of primary metabolism, and low energetic cost of the production of the natural products. In some cases the enzymes responsible for the production of natural products are functionally redundant and substrate tolerant, but this is highly variable across species and natural products.

What is less variable is the energy cost of production of natural products. This is one of the key tenets of proposal 6. The high metabolic cost of producing natural products indicates that they must have some value to the organism producing them. The great structural diversity, generally high concentrations of natural product in some parts of the organism, high biological activity and the nature of that activity, different species often produce the same (or very similar) natural products all serve to demonstrate that it is likely that natural products perform some function beneficial to the organism producing them.

Further evidence for this function comes from soil organisms. It has been estimated that 1 g of surface soil contains the following populations: bacteria (10^6-10^8), actinomycetes (10^6-10^7), protozoa (10^5-10^6), fungi (10^4-10^6), and algae (10^4-5x10^4).9 It has also been shown that it is comparatively easy to establish a population of a new soil organism in a sterilised sample of soil as opposed to a soil sample that has an established indigenous fauna. These facts demonstrate a highly competitive environment. Considering the modes of action of many actinomycete derived natural products (antibacterial, inhibitory of DNA production, or similar direct action on primary metabolism) one can see how soil organism chemical agents may have evolved as part of a “chemical war” between soil organisms.

There is also a wealth of genetic evidence that supports this hypothesis. For example the clustering of genes on the natural product biosynthesis pathway with genes that code for resistance to antibiotics. In this case an organism that produces a cytotoxic, antibiotic natural product would be strongly selected against should it fall victim to its own toxin. Genes that code for antibiotic resistance are also found in nature in species that do not produce antibiotic natural products themselves, but that co-exist with organisms that do.18-22

However, more relevant to medicine, and modern uses of natural products, is the often astonishing potency and specificity of bioactive natural products. This is also a key piece of evidence for the proposal that natural products provide some functional benefit to the organism that produces them. High specificity for a given substrate and biological activity, as mentioned above, are rare molecular traits. As these traits are rare, and as the specificity of interaction is so high, it is unlikely for these natural products to have arisen ex nihilo, add to that the fact that we find a gradual spectrum of natural product activities in nature, and you have a powerful argument in favour of hypothesis 6. An elegant example of this is the complementarity shown between the antibiotic vancomycin’s binding site and the cell wall peptide analogue N-acetyl-D-alanine-D-alanine. A schematic representation of this interaction is shown below in Scheme 3.i. 23-25

As has been mentioned, the chemical substances isolated from earth’s biota are astonishingly varied in structure and activity. Looking at the structures of polyketides shows that even in one biosynthetic class of natural products, the structural diversity is great. However, an examination of the structure of vancomycin, shown below in Scheme 3.i, one can see a mixed peptide/polyketide biosynthesis. Organisms also produce peptide natural products as an outgrowth of peptide synthesis in primary metabolism. These peptide natural products target similar primary metabolic processes to the non-peptide based natural products discussed above.



Scheme 3.i Schematic Representation of the Interaction between Vancomycin and a Bacterial Cell Wall Peptide Model

This is an important point to note, it would appear that organisms have evolved a variety of very different natural products to do a similar series of jobs. This not only provides yet more evidence for the hypothesis that natural products have evolved for specific functions, but it has important implications for medicine, and drug development.

Peptide natural products such as nostacyclamide (2), a potent antimicrobial, telomestatin (3), a telomerase inhibitor and potential anticancer lead, diazonamide, an anticancer target, (4) and the mixed peptide/polyketides ulapualide (5), an antifungal anticancer compound and phorboxazole (6), one of the most potent anticancer cytotoxins yet discovered, show not only some of the wide structural diversity mentioned, but also some of the most useful bioactivity yet found in natural products. This selection of natural products has been chosen to illustrate just some of the structural diversity found in peptide, and mixed polyketide/peptide natural products. The five natural products are derived from very different species, but they achieve roughly the same ends in nature, albeit with different modes of action. They all inhibit cell proliferation either by directly destroying the cell itself (nostacyclamide (2) and ulapualide (5)), or by acting in such a way as to interrupt DNA synthesis in the cell (diazonamide (4), ulapualide (5), and phorboxazole (6)), or by preventing cancer cells from being extremely long lived due to a quirk of their DNA repair mechanisms (telomestatin (3)).



Nostacyclamide (2), Telomestatin (3), Diazonamide (4) Ulapualide (5) and Phorboxazole (6)

Because the biological origins of these natural products, their structure related biological activity and their biosynthesis are so intimately and inextricably linked, understanding how natural products have evolved is a key part of understanding their structure-activity relationship, and thus is a cornerstone of both developing new treatments and our understanding of the natural world. Whilst the precise evolutionary origins and utility of natural products remain reasonably disputed matters, a large body of work has shown precisely how these natural products are synthesised in nature.

4.Bibliography

1 J. Mann, Magic, Murder and Medicine, Oxford University Press, 2000.

2 J. E. Page, M. A. Huffman, V. Smith, and G. H. N. Towers, Journal of Chemical Ecology, 1997, 23, 2211-2226.

3 A. Fleming. On the Antibacterial Action of Cultures of Penicillium, With Special Reference to Their Use in the Isolation of B. Influenzae. The British Journal of Experimental Pathology 10, 226-236. 1929.

4 F Wöhler. On the Artificial Production of Urea. Annalen der Physik und Chemie 88, 253. 1828.

5 M. S. Lesney. Nature's Pharmaceuticals. Today's Chemists at Work July, 26-32. 2004.

6 M. G. Watve, R. Tickoo, M. M. Jog, and B. D. Bhole, Archives of Microbiology, 2001, 176, 386-390.

7 R. D. Firn and C. G. Jones, Natural Product Reports, 2003, 20, 382-391.

8 R. D. Firn and C. G. Jones, Molecular Microbiology, 2000, 37, 989-994.

9 R. A. Maplestone, M. J. Stone, and D. H. Williams, Gene, 1992, 115, 151-157.

10 M. J. Stone and D. H. Williams, Molecular Microbiology, 1992, 6, 29-34.

11 L. C. Vining, Annual Review of Microbiology, 1990, 44, 395-427.

12 D. H. Williams, M. J. Stone, P. R. Hauck, and S. K. Rahman, Journal of Natural Products, 1989, 52, 1189-1208.

13 G. Cimono and Ghiselin M.T., Marine Natural Products As and Evolutionary Narrative, in Marine Chemical Ecology, CRC, 2001, pp. 115-155.

14 B. B. Jarvis and J. D. Miller, Natural Products, Complexity and Evolution, in Phytochemical Diversity and Redundancy in Ecological Interactions, ed. Romeo et al, Plenum Press, New York, 1996, pp. 265-293.

15 B. B. Jarvis, The Role of Natural Products in Evolution, in Evolution of Metabolic Pathways, ed. J. T. e. a. Romeo, Elsevier, 2000, pp. 1-24.

16 E. Mayr, Towards a New Philosophy of Biology: Observations of an Evolutionist, Harvard University Press, Boston, 1989.

17 C. G. Jones and R. D. Firn, Philosophical Transactions of the Royal Society of London Series B-Biological Sciences, 1991, 333, 273-280.

18 C. J. Thompson, D. Fink, and L. D. Nguyen, Genome Biol., 2002, 3, 1020.

19 G. L. Challis and D. A. Hopwood, Proceedings of the National Academy of Sciences of the United States of America, 2003, 100, 14555-14561.

20 S. D. Bentley, K. F. Chater, A. M. Cerdeno-Tarraga, G. L. Challis, N. R. Thomson, K. D. James, D. E. Harris, M. A. Quail, H. Kieser, D. Harper, A. Bateman, S. Brown, G. Chandra, C. W. Chen, M. Collins, A. Cronin, A. Fraser, A. Goble, J. Hidalgo, T. Hornsby, S. Howarth, C. H. Huang, T. Kieser, L. Larke, L. Murphy, K. Oliver, S. O'Neil, E. Rabbinowitsch, M. A. Rajandream, K. Rutherford, S. Rutter, K. Seeger, D. Saunders, S. Sharp, R. Squares, S. Squares, K. Taylor, T. Warren, A. Wietzorrek, J. Woodward, B. G. Barrell, J. Parkhill, and D. A. Hopwood, Nature, 2002, 417, 141-147.

21 S. Omura, H. Ikeda, J. Ishikawa, A. Hanamoto, C. Takahashi, M. Shinose, Y. Takahashi, H. Horikawa, H. Nakazawa, T. Osonoe, H. Kikuchi, T. Shiba, Y. Sakaki, and M. Hattori, Proceedings of the National Academy of Sciences of the United States of America, 2001, 98, 12215-12220.

22 J. G. Burgess, E. M. Jordan, M. Bregu, A. Mearns-Spragg, and K. G. Boyd, Journal of Biotechnology, 1999, 70, 27-32.

23 J. P. Waltho, D. H. Williams, D. J. M. Stone, and N. J. Skelton, Journal of the American Chemical Society, 1988, 110, 5638-5643.

24 J. P. Waltho, J. Cavanagh, and D. H. Williams, Journal of the Chemical Society-Chemical Communications, 1988, 707-709.

25 D. H. Williams and J. P. Waltho, Biochemical Pharmacology, 1988, 37, 133-141.

5. Notes Added In Edit

A) Wikipedia has reasonable entries on secondary metabolites and natural products. The terms are used interchangeably in modern organic chemistry, perhaps if I'm being pedantic I'd say this was a bit sloppy of us, but there is a high degree of accuracy to their interchange and the anal retentive technical semantics of my field are far from exciting!

B) Speaking of technical wrangles in scientific fields, I freely admit that the above is massively over emphasising adaptation. As we are mostly dealing with microorganisms I think that horizontal gene transfer and simple genetic drift have a greater part to play. However, I haven't scoured the lit for this distinction over the last 2 or so years and I didn't find much on it the first time around. I may point Larry Moran at this and see what he knows because the evolution of bioactive secondary metabolites is a very important topic, and if I'm right about a few things (research proposals are being written) then secondary metabolites and secondary metabolism in certain species have big clues about certain stages of abiogenesis. And no I won't be more specific until I have some evidence!

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Bye.

  
Louis



Posts: 6436
Joined: Jan. 2006

(Permalink) Posted: May 11 2007,14:55   

Hmmmm editing and formatting haven't worked, and the images are horrible. I'll have to go back and edit it a bit later. Apologies.

Louis

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J-Dog



Posts: 4402
Joined: Dec. 2006

(Permalink) Posted: May 11 2007,15:00   

Cool - very Sciencey!  I had to click on the links though to see the pictures.  I really am not qualified to comment on your work further, but it looks to me like you know your chem, dude!

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Come on Tough Guy, do the little dance of ID impotence you do so well. - Louis to Joe G 2/10

Gullibility is not a virtue - Quidam on Dembski's belief in the Bible Code Faith Healers & ID 7/08

UD is an Unnatural Douchemagnet. - richardthughes 7/11

  
Albatrossity2



Posts: 2780
Joined: Mar. 2007

(Permalink) Posted: May 11 2007,15:11   

Louis

Nice overview.  When was this written?

I also note that you mentioned one of my favorite molecules, Taxotere™ (derived from the plant metabolite known as Taxol). I discussed this chemotherapeutic drug in one of my previous interactions with FtK (when I was still being "nice" according to her standards), because it is an excellent example of how common descent was absolutely critical in the development of a medical treatment. Of course, Dr. Egnor and Barrister Luskin don't understand that, and since FtK thinks that they are excellent evolutionary science experts, she dismisses it as well.

Good work.

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Flesh of the sky, child of the sky, the mind
Has been obligated from the beginning
To create an ordered universe
As the only possible proof of its own inheritance.
                        - Pattiann Rogers

   
Arden Chatfield



Posts: 6657
Joined: Jan. 2006

(Permalink) Posted: May 11 2007,15:38   

Louis:

Quite nice, and very readable as these things go. :)

If you don't mind my asking, what was the title, and what university did you write it at?

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"Rich is just mad because he thought all titties had fur on them until last week when a shorn transvestite ruined his childhood dreams by jumping out of a spider man cake and man boobing him in the face lips." - Erasmus

  
Louis



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Joined: Jan. 2006

(Permalink) Posted: May 11 2007,17:48   

Thanks guys. I'll sort the formatting out tomorrow morning and give it a quick edit, I really just C+Ped a bit of an old version of parts of two sections of intro and welded them together.

It was written in late 2005, the institution and title will have to remain untold for the moment I'm afraid, mainly due to the nature of the organisation who funded the work and some of the more productive results (this should make some things obvious to the cognoscenti!).

Louis

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Bye.

  
Louis



Posts: 6436
Joined: Jan. 2006

(Permalink) Posted: May 11 2007,18:06   

Albatrossity2,

It's not really an overview, I did a synthetic chem PhD so it's really the padding/intro blurb used to set the scene. I got into trouble for trying to do a proper overview for a recent review article because I went far far beyond the scope of the remit I was given. It's a subject I love and have some ideas about, and if I decide to get out of industry and go back and postdoc again (and hopefully one day get my own group)  I see a valuable few questions I could work on. Pipe dreams for the moment though {sigh}.

Your Taxol example is great, especially because as you note the semi-synthesis of Taxol is possible from 11-deacyl baccatin which is much more readily available from European Yew leaves (common) as opposed the footling amounts of Taxol found in Pacific Yew Bark (rare and you have to kill the tree to get it). A synthetic chemistry joke in our lab (and probably many others) to our Taxol boys was that in the three years they'd been slogging in the lab they didn't even make one mg of Taxol, the tree had made about 6. So they were not as good a chemist as a Pacific Yew tree. However, they then pointed out that in my case I was being thrashed by a Streptomyces. Cheeky fuckers (the Streptomyces that is)! Oh and there are several syntheses of Taxol out there, notably those early ones of Bob Holton and KC Nicolaou. None of them are really preparative though and considering the quantities of Taxol needed, totally hilariously useless in a process chemistry sense, which is why semisynthesis is the best available option.

I really want to sort that picture of Maitotoxin out (see here for a clear structure) it's one of my favourite molecules. It's a beast of thing and Nicolaou has a great piece about his work towards it in this week's Angewante Chemie. Although I am a little disillusioned with total synthesis as a concept/research field at the moment (the lab work is second to none) and I think it is ready for a good bit of revolution. We know we can make things, making things is no longer good enough, we need to make them spectacularly well.......ooooooops sorry I've drifted into extremely boring personal concerns about my field! Bad Louis!

Louis

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Bye.

  
skeptic



Posts: 1163
Joined: May 2006

(Permalink) Posted: May 11 2007,18:18   

Oh No, Louis!  You just sidetracked me.  I will probably spend hours on this.  Thanks for the post, though, this is wonderful stuff.

  
"Rev Dr" Lenny Flank



Posts: 2560
Joined: Feb. 2005

(Permalink) Posted: May 11 2007,19:00   

Quote (Louis @ May 11 2007,17:48)
It was written in late 2005, the institution and title will have to remain untold for the moment I'm afraid, mainly due to the nature of the organisation who funded the work

You mean The International Atheistic Conpsiracy to Do Really Really Bad Things?

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Editor, Red and Black Publishers
www.RedandBlackPublishers.com

  
Arden Chatfield



Posts: 6657
Joined: Jan. 2006

(Permalink) Posted: May 11 2007,19:02   

Quote ("Rev Dr" Lenny Flank @ May 11 2007,19:00)
Quote (Louis @ May 11 2007,17:48)
It was written in late 2005, the institution and title will have to remain untold for the moment I'm afraid, mainly due to the nature of the organisation who funded the work

You mean The International Atheistic Conpsiracy to Do Really Really Bad Things?

Nah, I bet he's deep cover at the Discovery Institute.

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"Rich is just mad because he thought all titties had fur on them until last week when a shorn transvestite ruined his childhood dreams by jumping out of a spider man cake and man boobing him in the face lips." - Erasmus

  
stevestory



Posts: 10127
Joined: Oct. 2005

(Permalink) Posted: May 11 2007,19:03   

This is an excellent post. It is exactly the kind of thing AtBC could use more of. Do you think we need a group blog, of the top dozen or so commenters here?

EDIT: I don't wan to step on Louis's thread, so I'll start a new one.

   
Arden Chatfield



Posts: 6657
Joined: Jan. 2006

(Permalink) Posted: May 11 2007,19:21   

This reminds me of an article I read somewhere long ago where they were discussing the possible evolutionary origin of psychoactive drugs in plants. I would assume everything you're saying here would apply to that as well, tho I doubt that FTK would say that the same stern Protestant God who gave us plants with medicine in them was the same one who is responsible for ergot and THC.  :p

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"Rich is just mad because he thought all titties had fur on them until last week when a shorn transvestite ruined his childhood dreams by jumping out of a spider man cake and man boobing him in the face lips." - Erasmus

  
Henry J



Posts: 4565
Joined: Mar. 2005

(Permalink) Posted: May 11 2007,22:37   

Re "bacteria (106-108), actinomycetes (106-107), protozoa (105-106), fungi (104-106), and algae (104-5x104).'

I'm wondering if there's supposed to be exponential operators inside those numbers? i.e., 10^6-10^8, etc.

Henry

  
Louis



Posts: 6436
Joined: Jan. 2006

(Permalink) Posted: May 12 2007,01:58   

Arden and Lenny,

Damn cover blown. I am a top secret, some might even say DOUBLE SECRET, agent of the EAC (which doesn't exist) inside the DI. Well I would be if the EAC existed. Which it doesn't. It's a ridiculous idea. A global conspiracy of evil atheists who torture kittens and drown puppies and prevent asinine bullshit posing as science dreamt up by drivelling idiots at the DI getting published in real journals and who hate the baby Jesus and persecute christians in their sleep? Nonsense. No such thing exists.

Stay where you are. Our black helicopters will not in any way be arriving with their jack booted occupants who will not under any circumstances take you away for questioning and memory re adjustment.

Louis (Not a member of the EAC at all, and definitely not the head of the Interesting Chemicals and Kitten Burning Department. Because it doesn't exist)

P.S. Henry, yes there should be exponents, I'm fixing the formatting this morning, I just C and Ped it from Word so lost the lot.

P.P.S. Arden, yes and no. IIRC Ergot alkaloids* are derived from ergot fungi growing on rye (i.e. not the plant itself) and are secondary metabolites, THC is I think (I'll have to check) a primary metabolite/plant hormone.

* I'm sure every one is familiar with the witch trials of medieval Europe. One of the causes proposed for bouts of mass hysterical witch burning etc is ergotamine/ergot alkaloid poisoning by fungal infected rye bread in rural communities. Basically these people were ripped to the tits on LSD like compounds and went ape shit. I had some really good papers on this somewhere but I can't find them, I'll dig them out if I can.

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Bye.

  
Louis



Posts: 6436
Joined: Jan. 2006

(Permalink) Posted: May 12 2007,02:37   

Hi All,

Right I've edited the above at little and sorted out the images. The last one is still a bit crap so I might have to redo it.

I hope the formatting makes things a little clearer, since I can't find superscript commands I've italicised the refernce marks.

HTH

Louis

P.S. Added in edit: Sorry to bring this up but I "ChemDrew" that Maitotoxin structure because at the time getting a good image of it the right size etc wasn't possible. It was a brief labour of love! It is, as far as I am concerned, an image of sheer hard core chemistry porn. I realise I am firmly outing myself (again) as a deviant chemistry geek with this, but I defy any chemically literate individual not to get wood (or lady-wood) over that monstrous molecule. It's the largest non biopolymeric molecule isolated to date, molecular weight of 3422, and it has an LD50 of around 50ng. That's right nanograms. That means it is sufficiently cytotoxic that a gram of it can kill roughly half a billion mice. Mmmmmmm dead mice!

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Reciprocating Bill



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Joined: Oct. 2006

(Permalink) Posted: May 12 2007,02:45   

Louis,

We're not going to take the bait. You’re asking us to play a game: “Provide as much detail in terms of possible causal mechanisms for your ID position as I do for my Darwinian position.” ID is not a mechanistic theory, and it’s not ID’s task to match your pathetic level of detail in telling mechanistic stories. If ID is correct and an intelligence is responsible and indispensable for certain structures, then it makes no sense to try to ape your method of connecting the dots. True, there may be dots to be connected. But there may also be fundamental discontinuities, and with IC systems that is what ID is discovering.

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Myth: Something that never was true, and always will be.

"The truth will set you free. But not until it is finished with you."
- David Foster Wallace

"Here’s a clue. Snarky banalities are not a substitute for saying something intelligent. Write that down."
- Barry Arrington

  
Louis



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Joined: Jan. 2006

(Permalink) Posted: May 12 2007,02:56   

Bill,

Gosh. How could I have been so blind all these years?

Of course you don't have to match my pathetic level of detail. My bad. All hail the Designer....whatever it is.

Louis

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nuytsia



Posts: 131
Joined: June 2006

(Permalink) Posted: May 12 2007,03:19   

Hi Louis,

Interesting post. (nice tidy up as well). But I'm not sure if I followed your points fully but I think my thinking might be slightly warped as I'm a botanist and my chemistry studies were soooooo long ago.
Your comparison of metabolites with the immune system kind of falls over for me as I seem the immune system as being purely against parasites, whereas metabolites can do this as well as dissuade other organism from eating you or (in the case of excretion) nobbling your competition.
Am I missing something here?
Sorry if this sounds dense.

Saw a rather nice figure a few years ago on chemical evolution in Apiaceae. As I recall the figure showed a series of increasingly complex defensive molecules and showed the number of species (and genera, i think) that used them.
It was a nice little curve. I'm sure it's in one of my books I'll see if I can dig it up.

In relation to your point on not poisoning yourself with your own toxins, I'm reminded of the observation that a fair number of mistletoe species often grow on other mistletoes and/or plants within the same order (Santalales). The records I have are fairly patchy I'll be honest, but I'm surprised at how often it's recorded and had come to the assumption that metabolite compatibility might be a reason for this.

I hadn't heard about THC being a plant hormone. Again I assumed it was purely defensive particularly in light of the fact that it builds up to it's highest levels in the female inflorescences - to protect the seed one assumes?

   
Louis



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Joined: Jan. 2006

(Permalink) Posted: May 12 2007,03:43   

Hi Nuytsia,

Quote
Your comparison of metabolites with the immune system kind of falls over for me as I seem the immune system as being purely against parasites, whereas metabolites can do this as well as dissuade other organism from eating you or (in the case of excretion) nobbling your competition.
Am I missing something here?


Probably not! ;-)

The analogy I was making was that in animal immune systems lots of different antibodies can be made very cheaply. This massive diversity of antibodies means that the immune system is "primed" against many different attacks at relatively little cost to the organism. The analogy is that a similar massive diversity of bioactive secondary metabolites exists in certain microorganisms (i.e. in just one organism, for example Streptomyces coelicolor) and that this diversity, like that of the immune system, "primes" the organism against many different attacks. I wasn't intending to suggest that secondary metabolites = proto immune system (although this has been proposed) or that they share an identical function. The major difference, for the purposes of the analogy, between immune antibodies and secondary metabolites is that secondary metabolites aren't cheap in terms of their energy cost to the organism. The analogy is focussed on the diversity of structure and function of secondary metabolites and antibodies, not the whole immune system.

Thanks for the info about mistletoes and Apiaceae and you're right about THC being a secondary metabolite and not a hormone. Thanks for correcting me on that, I wasn't sure about the primary metabolite thing anyway. Here's a reference:

Taiz, L. and Zeiger, E. 1991. Plant Physiology

Cheers

Louis

--------------
Bye.

  
nuytsia



Posts: 131
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(Permalink) Posted: May 12 2007,04:16   

Ah!
Cool.  :)

   
Ftk



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(Permalink) Posted: May 12 2007,09:03   

Louis, I really like this topic.  Your post is very interesting, and I've got a couple questions to ask.  I read through you article twice last night and jotted down a few things, but I'll have to read through it two more times in order to try to absorb all of it into my tiny little unscientific brain. ;)

After I do that, I'll ask my questions.  I may not get them posted until Sunday or Monday because I have 4 friggin' ball games to sit through today, and tonight is my 6th grader's big party with his classmates.  They head off to junior high next year.  Yikes!  My baby is growing up...

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"Evolution is a creationism and just as illogical [as] the other pantheistic creation myths"  -forastero

  
Ftk



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(Permalink) Posted: May 12 2007,09:23   

BTW, is there any possible way to keep Lenny & Oldman from posting to this thread?

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"Evolution is a creationism and just as illogical [as] the other pantheistic creation myths"  -forastero

  
"Rev Dr" Lenny Flank



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(Permalink) Posted: May 12 2007,09:42   

Quote (Ftk @ May 12 2007,09:23)
BTW, is there any possible way to keep Lenny & Oldman from posting to this thread?

Why?  Don't like the questions we keep asking you?

I, uh, thought you weren't here to discuss science, anyway.  Change your mind, didja?

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"Rev Dr" Lenny Flank



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(Permalink) Posted: May 12 2007,10:06   

Quote (Ftk @ May 12 2007,09:03)
Louis, I really like this topic.  Your post is very interesting, and I've got a couple questions to ask.  I read through you article twice last night and jotted down a few things, but I'll have to read through it two more times in order to try to absorb all of it into my tiny little unscientific brain. ;)

After I do that, I'll ask my questions.  I may not get them posted until Sunday or Monday because I have 4 friggin' ball games to sit through today, and tonight is my 6th grader's big party with his classmates.  They head off to junior high next year.  Yikes!  My baby is growing up...

What FTK is actually trying to say, of course, is that she doesn't understand a single thing you are saying, so she's going to search around for some creationist tract or another that discusses something that she thinks is vaguely similar, and then parrot all the "devestating questions for evolutionists" that she finds within.


Of course, she won't understand any of the answers, either.  (shrug)

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Reciprocating Bill



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(Permalink) Posted: May 12 2007,10:30   

Louis -

Although not remotely qualified to comment upon the chemistry and biology that provide the foundations for your research, I can recognize the machinery of genuine scientific inquiry in motion.  You've immersed yourself in and absorbed a large prior research literature and the corresponding theoretical framework, reported/generated hypotheses that emerge from that theory and research, and (I've no doubt) gone on to describe/devise/report experimental procedures of sufficient power to test some element of that nexus of general theory and specific hypothesis. Publication and peer review are not ends in of themselves; rather, they are gateways through which your research may join a larger conversation within your particular research community and advance the cumulative "distributed cognition" that is science.  

In short, there is more science in your dissertation, and its potential connections to the scientific conversation within your field, than within the ENTIRETY of the intelligent design literature.  

FTK -

It follows that Louis' research only takes on meaning within the context of contemporary biological science, and specifically evolutionary biology.  The latter, in turn, are embedded in a vast network of contemporary physical, chemical, geological, paleontological, historical and biological observation, the implications of which you reject. Holding to a young earth, rejection of common ancestry, etc. entail the rejection of that entire network, including the specific conceptual bases for Louis' inquiry, which is thoroughly and intrinsically evolutionary in nature. So it is beyond me why Louis' research would have the slightest interest to you - unless that larger network, and the promise of progressively increased understanding of the natural world leveraged by evolutionary biology, also beckon.

--------------
Myth: Something that never was true, and always will be.

"The truth will set you free. But not until it is finished with you."
- David Foster Wallace

"Here’s a clue. Snarky banalities are not a substitute for saying something intelligent. Write that down."
- Barry Arrington

  
Ftk



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(Permalink) Posted: May 12 2007,10:40   

Quote
Holding to a young earth, rejection of common ancestry, etc. entail the rejection of that entire network, including the specific conceptual bases for Louis' inquiry, which is thoroughly and intrinsically evolutionary in nature. So it is beyond me why Louis' research would have the slightest interest to you - unless that larger network, and the promise of progressively increased understanding of the natural world leveraged by evolutionary biology, also beckon.


God, you people are infuriating.  Is it so utterly hard to understand that some people are looking for answers and that they are open minded to everything?  

I think the ToE is a fascinating subject.  A person doesn't have to be completely 100% convinced that something is a fact beyond all reasonable doubt to find topic interesting to read about.  

So, let me get this straight, you feel that if a person is open minded to the possibility of a YE, they never again read about anything that might negate that viewpoint?  Is that what you think?  If so, then you're crazy.

--------------
"Evolution is a creationism and just as illogical [as] the other pantheistic creation myths"  -forastero

  
Ftk



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(Permalink) Posted: May 12 2007,10:46   

Quote
What FTK is actually trying to say, of course, is that she doesn't understand a single thing you are saying, so she's going to search around for some creationist tract or another that discusses something that she thinks is vaguely similar, and then parrot all the "devestating questions for evolutionists" that she finds within.


Someone better get this asshole off the thread, or I'm done.  

FYI, I have already had questions in my mind about this topic before Louis even brought it up.  That is why I mentioned it on another thread.  Obviously, there are parts of the article that I don't completely understand so I'd like to take the time to read it thoroughly again before I post.  Is that okay, freak boy?  And, no, I'm not frantically checking creation websites for Q&A's.  I'm leaving in 15 minutes for a ball game.

Someone please get this freak off the thread.

--------------
"Evolution is a creationism and just as illogical [as] the other pantheistic creation myths"  -forastero

  
"Rev Dr" Lenny Flank



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(Permalink) Posted: May 12 2007,10:47   

Quote (Ftk @ May 12 2007,10:40)
open minded to everything?  

Are you also "open-minded" to the concept of a flat earth?

Are you "open-minded" to the evil-spirits theory of disease?

Are you "open-minded" about geocentrism as opposed to heliocentrism?

What about polytheism as opposed to monotheism -- are you "open-minded" about that?

Are you "open-minded" about Catholicism vs Protestantism?

How about the idea that the Bible wasn't written by God, but was written by a bunch of humans who thought God was talking to them.  Are you, uh, "open-minded" about that, too?

Or are you just, uh, awfully selective about what you're "open-minded" about . . . . . .

--------------
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www.RedandBlackPublishers.com

  
"Rev Dr" Lenny Flank



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(Permalink) Posted: May 12 2007,10:50   

Quote (Ftk @ May 12 2007,10:46)
Someone better get this asshole off the thread, or I'm done.  

Bye.  (shrug)

This isn't your blog, FTK.  Unlike on your blog, you don't get to censor people here, or prevent them from asking you things that you don't like.  And if you can't take that, then go back to your safe and secure little hidey hole where you can control everything that goes on around you.

I apologize for hijacking Louis's thread, but I am quite sure he underdstand why, and agrees with me.

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Ftk



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(Permalink) Posted: May 12 2007,10:54   

Fine, Lenny.

I'm done here.

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"Evolution is a creationism and just as illogical [as] the other pantheistic creation myths"  -forastero

  
"Rev Dr" Lenny Flank



Posts: 2560
Joined: Feb. 2005

(Permalink) Posted: May 12 2007,10:55   

Quote (Ftk @ May 12 2007,10:40)
I think the ToE is a fascinating subject.  A person doesn't have to be completely 100% convinced that something is a fact beyond all reasonable doubt to find topic interesting to read about.  

FTK, are you, uh, lying to us when you say that you ARE here to discuss science with us, or are you lying to us when you say you're NOT here to discuss science with us . . . . . ?

Which is it?  Make up your frigging mind.

--------------
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"Rev Dr" Lenny Flank



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(Permalink) Posted: May 12 2007,10:56   

Quote (Ftk @ May 12 2007,10:54)
Fine, Lenny.

I'm done here.

Again?

--------------
Editor, Red and Black Publishers
www.RedandBlackPublishers.com

  
Reciprocating Bill



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(Permalink) Posted: May 12 2007,11:05   

Quote (Ftk @ May 12 2007,10:40)
So, let me get this straight, you feel that if a person is open minded to the possibility of a YE, they never again read about anything that might negate that viewpoint?  Is that what you think?  If so, then you're crazy.

Embrace of a young earth certainly necessarily entails the rejection of the network to which I refer. It follows that the embrace of a YE would render Louis' work meaningless, because one will have rejected the entire framework within which his work is grounded, and leveraged. That may not characterize you - as I said, you may find that genuine science also beckons.

That said, your open mindedness to the the possibility of a YE certainly entails openness to the rejection of that network.  You won't be able to have it both ways.

--------------
Myth: Something that never was true, and always will be.

"The truth will set you free. But not until it is finished with you."
- David Foster Wallace

"Here’s a clue. Snarky banalities are not a substitute for saying something intelligent. Write that down."
- Barry Arrington

  
"Rev Dr" Lenny Flank



Posts: 2560
Joined: Feb. 2005

(Permalink) Posted: May 12 2007,12:12   

Louis, I now respectfully turn your thread back over to you.

In the immortal words of Han Solo, "Sorry about the mess."



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Ichthyic



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(Permalink) Posted: May 12 2007,12:23   

Quote
As we are mostly dealing with microorganisms I think that horizontal gene transfer and simple genetic drift have a greater part to play.


that entirely depends on the localized conditions, especially with such rapid generation times.

selection pressures can have a profound effect over several generations and be an obvious factor, or you could have what appears to be a relatively minor selection event trigger a huge change in direction.

Don't spend too much time in the micro lit. without exploring the organismal lit.;  you'll find the lab boys spend way to much time thinking their environments are completely controlled for selective pressures, and thereby overestimate the role of drift.

horizontal transfer complicates the picture, but also doesn't necessarily limit the role a specific selection pressure can play.

I've always looked at horizontal transfer as more a mechanism of generating variability, much like a "psuedo-sex" (so what would an oncovirus be?).

selection still acts on the end result.

--------------
"And the sea will grant each man new hope..."

-CC

  
Reciprocating Bill



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Joined: Oct. 2006

(Permalink) Posted: May 12 2007,12:28   

Quote ("Rev Dr" Lenny Flank @ May 12 2007,12:12)
Louis, I now respectfully turn your thread back over to you.

In the immortal words of Han Solo, "Sorry about the mess."


Dude! That photo is from the sanitized and corrected Star Wars, in which the green thing fires first and Han Solo takes it out in self defense.

In the original, Solo greases the thing outright.

--------------
Myth: Something that never was true, and always will be.

"The truth will set you free. But not until it is finished with you."
- David Foster Wallace

"Here’s a clue. Snarky banalities are not a substitute for saying something intelligent. Write that down."
- Barry Arrington

  
"Rev Dr" Lenny Flank



Posts: 2560
Joined: Feb. 2005

(Permalink) Posted: May 12 2007,12:31   

Quote (Reciprocating Bill @ May 12 2007,12:28)
Quote ("Rev Dr" Lenny Flank @ May 12 2007,12:12)
Louis, I now respectfully turn your thread back over to you.

In the immortal words of Han Solo, "Sorry about the mess."


Dude! That photo is from the sanitized and corrected Star Wars, in which the green thing fires first and Han Solo takes it out in self defense.

In the original, Solo greases the thing outright.

Yes, I know ---- HAN SHOT FIRST !!!!!!!!!!!!!!!!!

I always hated that change.  It detracts from the Han Solo character, who IS, at that point, a scoundrel, after all . . .

--------------
Editor, Red and Black Publishers
www.RedandBlackPublishers.com

  
Reciprocating Bill



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(Permalink) Posted: May 12 2007,13:08   

Quote ("Rev Dr" Lenny Flank @ May 12 2007,12:31)
...I always hated that change.  It detracts from the Han Solo character, who IS, at that point, a scoundrel, after all . . .

Done "for the kids," naturally.  
(*snort*)

--------------
Myth: Something that never was true, and always will be.

"The truth will set you free. But not until it is finished with you."
- David Foster Wallace

"Here’s a clue. Snarky banalities are not a substitute for saying something intelligent. Write that down."
- Barry Arrington

  
"Rev Dr" Lenny Flank



Posts: 2560
Joined: Feb. 2005

(Permalink) Posted: May 12 2007,13:17   

Quote (Reciprocating Bill @ May 12 2007,13:08)
Done "for the kids," naturally.  
(*snort*)

Next thing ya know, they'll be burning library books.  Again.

--------------
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www.RedandBlackPublishers.com

  
Louis



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(Permalink) Posted: May 12 2007,14:18   

FTK,

Please go right ahead and ask any questions you like and I'll do my best to answer them.

Don't let the fun with Lenny and me and others distract you. We are a tetchy and easily annoyed bunch (me especially). The sad thing is we've all seen too many creationists and ID creationists and false little religious weasels hiding behind nice words. It can make people a little shell shocked and unsympathetic. Hell, Lenny on a bad tolerance day makes my good days look like a war zone, tolerant of fools I am not, Lenny's a pussy cat (a very well informed pussy cat by the way, never ignore that) by comparison.

I have quit discussing science with people like you (not an insult, unless I want to insult my own parents, who while not religious are curious, occasionally confused, intelligent and relatively scientifically uninformed. I assure you I DON'T want to insult them or you...at least not right now!) in the past, and if I'm honest I've been thinking about quitting again recently. It does take up some time, not a huge amount, but that time could be more productively spent. I'm also not beyond admitting that I do get very annoyed by some of the bullshit I have to put up with.

However, that said, I love what I do and I love talking about it. I'm a very passionate scientist and recent months of internet conversation have been unproductive and pretty unpleasant, mainly because I get frustrated with some of the petty idiots I have encountered. Why bother I ask myself? (I blame myself for this btw, not other people. If I were more tolerant and a better communicator then.....well you get the picture)

But then I encounter someone like Steve Elliot who is genuinely curious, and I know why I bother. It's a pleasure to talk to someone like that, not because they agree with me, or join the in-crowd, or see the light or anything so stupid and fictional as that, but because they actually are as excited and curious about the universe around them as I am. That curiosity isn't satisfied with answers because answers breed more questions.

We humans have a set of techniques and methods by which we interrogate the universe around us on a daily basis. We all use them all the time. You'll have to trust me on this for the moment, but ID, creationism, much of religious thought, dogmatic ideologies like some types of communism and other totalitarian political ideologies and all things like them are the result of the abandonment of these techniques and processes. They are the very antithesis of these processes, they are quite truly anathema to them. The reasons people abandon these techniques and methods are multifarious and sometimes profound but not a single one of the reasons is reasoned! (Forgive the pun) This is a hard fact to accept but it is demonstrably true beyond all reasonable doubt. Anyway I've rambled off somewhere!

I hope you are genuinely curious as you claim to be, and I hope you come back with genuine questions not recycled creationist garbage. Sorry if my lack of faith in your intentions offends you but you haven't exactly been little miss science and curiosity since you've come here! You can blame us big ol' meanies all you like, but try to take some responsibility for your own actions. Perhaps, just perhaps, FTK you need to work on YOUR approach too. Just a thought.

Anyway, all that crap aside, please go ahead and ask your questions. Genuine curiosity will always be met with genuine answers and civility. Creationist drivel, religious irrelevances, childish point scoring, illogical nonsense and all round silliness won't be. Sounds like a fair trade to me, but then I'm biased right? ;-)

Louis

--------------
Bye.

  
skeptic



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(Permalink) Posted: May 13 2007,22:56   

Louis, you've definitely outed me and I'll admit to semi-wood.  50 ng was the kicker!

Ftk, if you're still there, go ahead and ask any serious questions to Louis.  He'll answer them and maybe with only a minimum of colorful adjectives.  Or you could ask me and I'll include no adjectives.  As for the rest, you'll just have to accept that they'll stand-by and comment as they see fit.  My advice is to ignore the extraneous stuff and stay on topic.  All knowledge comes with sacrifice so just consider this your trial, if you're really interested in learning about this topic and science in general.  Good luck and I hope you try, it will be to your benefit and it is certainly worth some harsh words.

whew, 50 ng...!

  
Ichthyic



Posts: 3325
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(Permalink) Posted: May 14 2007,00:20   

Quote
Or you could ask me and I'll include no adjectives


HAHHAHAHA!

right.

and when I want to know about quantum dynamics, I'll ask my local gas station clerk.  I doubt he would use any colorful adjectives in describing the finer points of quantum dynamics either.

--------------
"And the sea will grant each man new hope..."

-CC

  
skeptic



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(Permalink) Posted: May 14 2007,00:32   

Have you got a synthesis, or even just a summarized version, of the massivetoxin (my name, lol)?  It defys belief that this is a fortuitous byproduct and not the primary product.  Isn't nature wonderful.

  
Louis



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(Permalink) Posted: May 14 2007,02:48   

Skeptic,

Maitotoxin has yet to be totally synthesised. However it is a "ladder polyether" type of polyketide and there are a lot of other molecules (not quite as big and gaudy) like it. Look up syntheses of brevetoxin B (Nicolaou et al., J. Am. Chem. Soc., 1995, 1171; and Nicolaou et al., J. Am. Chem. Soc., 1995, 1173) and palytoxin (Kishi et al., J. Am. Chem. Soc., 1989, 7525; Kishi et al., J. Am. Chem. Soc., 1989, 7530, Kishi et al., J. Am. Chem. Soc., 1994; 11205; Kishi et al., Chem. Scr., 1987, 573; and Kishi, Pure & Appl. Chem., 1989, 313.)

Nicolaou has something on Maitotoxin in the "soon to be published" section of the Angewante Chemie website, if you have access look it up. If you are interested in total synthesis you can do little better for a (very self centred) introduction to the topic by Nicolaou than "Classics in Total Synthesis" and its imaginatively titled sequel "Classics in Total Synthesis II".

I've asked you this before, Skeptic: you claimed once (IIRC) to be a chemist what sort of chemist are you? What's your background?

Louis

P.S. Do you still want to do this debate thingy?

--------------
Bye.

  
skeptic



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(Permalink) Posted: May 14 2007,07:47   

Louis, thanks for the references.  I have access to all but the online journal but the others should satisfy my curiousity.  Synthesis is something I find very interesting but I've struggled with (which is probably why I find it so interesting).

As far as my background, I have BSs in Chem and Computer Sci and MS in Medicinal Chem.  I've been away from the bench for about five years now.  Before that I did toxicology and environmental impact studies on industrial and pharmaceutical products and now I model toxicology and biologic activity.  All computer work and no lab play sometimes makes skeptic a sad boy.  Just to be fair, though, I do love what I do.

I'm still interested in the debate idea.  I think there are so many positives that can come from it even though my inner chemistry nerd would probably have more fun on this thread.

Ichy, what??? *with wide-eyed innocence*
I'm pretty sure that I can answer any question Ftk asks and even to your satisfaction.  And I can guarentee that I'll use a minimum of colorful adjectives.   :D

  
Louis



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(Permalink) Posted: May 14 2007,08:21   

Skeptic,

I'd be surprised if your workplace didn't have access to Wiley Interscience online. Angewante's not an insignificant obscure journal, it's as good (better IMO) as JACS. I've done a good bit of med chem, I spent 5 years doing med chem lab work and another couple supervising/interacting with it whilst doing process chem lab work.  

Anyway, that aside what's this fucking prejudice about colourful cunting adjectives? Swearing is GOOD. Never forget that ;-)

Louis

P.S. Only Semi-Wood? Might I suggest a few hundred mg of the citric acid salt of this compound:



--------------
Bye.

  
Paul Flocken



Posts: 290
Joined: Dec. 2005

(Permalink) Posted: May 14 2007,08:57   

Quote (Louis @ May 14 2007,08:21)
Skeptic,

Anyway, that aside what's this !@#$%^& prejudice about colourful !@#$%^& adjectives? Swearing is GOOD. Never forget that ;-){heavily redacted :D }

Louis


The heartburn that Dr. Elsberry has* over swearing is that he would like to think that PT and the related sites are good places for children to read about evolution.  Atleast I think I can remember him writing something such.  I suppose additionally, though I don't know how they work and therefore can't justify it, that nanny software will exclude a site that has such swearing.

Sincerely, Paul

*Not to overlook that Dr. Elsberry is also a good a proper Christian.

edit: that last was said without sarcasm though on second look it appeared to

--------------
"The great enemy of the truth is very often not the lie--deliberate, contrived, and dishonest, but the myth, persistent, persuasive, and unrealistic.  Belief in myths allows the comfort of opinion without the discomfort of thought."-John F. Kennedy

  
Louis



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(Permalink) Posted: May 14 2007,09:08   

I never fucking knew that.

I thought this was a bar, or at least the place where the really drunk people went after they'd been to the bar. Swearing-bar-bar-swearing. Beer, full frontal nudity (LENNY FOR THE FSM'S SAKE NO), swearing, casual violence and cheeky pig based crunchy snacks are surely par for the course (and yes I've read the rules....Damn!).

Louis

--------------
Bye.

  
"Rev Dr" Lenny Flank



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(Permalink) Posted: May 14 2007,18:13   

Quote (Louis @ May 14 2007,09:08)
full frontal nudity (LENNY FOR THE FSM'S SAKE NO),

(opens raincoat)

Too late.

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skeptic



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(Permalink) Posted: May 14 2007,20:54   

Quote (Louis @ May 14 2007,08:21)
Skeptic,


Louis

P.S. Only Semi-Wood? Might I suggest a few hundred mg of the citric acid salt of this compound:


mix that with some of this and the kids go crazy:


  
Louis



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(Permalink) Posted: May 15 2007,02:42   

Go crazy? Naaaah they die. Google "Saturday night fever" (you might have to hunt about a bit).

The combination of E or speed or coke and viagra is very hard work for the heart. When viagra first hit the streets ER doctors had several very healthy and fit young gentleman from the group of young gentlemen who like other young gentlemen come through their doors with massive coronary episodes and whacking great hard ons.

"Doc, Doc, Save me, I'm dying....but first look at THAT it's MAGNIFICENT!"

Hmmmm. We seem to have drifted.

Louis

--------------
Bye.

  
skeptic



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(Permalink) Posted: May 15 2007,13:45   

what can we say, chemistry jokes. lol

  
Reciprocating Bill



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(Permalink) Posted: May 16 2007,10:55   

Quote (skeptic @ May 15 2007,13:45)
what can we say, chemistry jokes. lol

If you aren't part of the solution, you're part of the precipitate.

(I think someone else around here posted that earlier).

--------------
Myth: Something that never was true, and always will be.

"The truth will set you free. But not until it is finished with you."
- David Foster Wallace

"Here’s a clue. Snarky banalities are not a substitute for saying something intelligent. Write that down."
- Barry Arrington

  
MidnightVoice



Posts: 380
Joined: Aug. 2005

(Permalink) Posted: May 16 2007,17:45   

Quote
Many of the antibodies produced by an organism’s immune system are currently redundant, they have evolved for antigens that they will never now encounter
 Specifc antibodies are produced in response to specific attacks, and "remembered" by the body for later use.  Hence vaccination works.  I don't think there are specific antibodies flaoting around from prehistoric time, but I maybe wrong.  So I am not sure if your statement is entirely accurate.

And one of my favorite molecule names is "Vomitoxin"  :D

--------------
If I fly the coop some time
And take nothing but a grip
With the few good books that really count
It's a necessary trip

I'll be gone with the girl in the gold silk jacket
The girl with the pearl-driller's hands

  
skeptic



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(Permalink) Posted: May 16 2007,20:56   

In simple terms, that's correct.  The initial immune response of IgA and IgG dwindle but the memory B and T cells remain and trigger the immune response at later exposure.

I'm going alittle out on a limb here but I think I recall some autoimmune disorders associated with a hyper-response in which these levels don't dwindle, but don't quote me on that one.

  
Henry J



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(Permalink) Posted: May 16 2007,21:34   

Re "If you aren't part of the solution, you're part of the precipitate."

Well, at least we got that ironed out before the mixture of elements bonded to compound the problem.

Henry

  
Louis



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(Permalink) Posted: May 17 2007,04:57   

Quote (MidnightVoice @ May 17 2007,00:45)
Specifc antibodies are produced in response to specific attacks, and "remembered" by the body for later use.  Hence vaccination works.  I don't think there are specific antibodies flaoting around from prehistoric time, but I maybe wrong.  So I am not sure if your statement is entirely accurate.

And one of my favorite molecule names is "Vomitoxin"  :D

I think the paper quoted (it's one of the Brown ones IIRC) refers not only to the antibodies we inherit via the placenta but (as Skeptic alludes to) the capabilities of our immune system to produce antibodies to threats we as individuals haven't encountered (perhaps yet) but we as an organism in a long chain of evolved organisms have. Meh, it probably needs rewording, cheers for pointing it out!

As for well named molecules, yes vomitoxin is a good one. there is an erotic acid which is always good for a chuckle, but the crowning glory has to go to the arsenic analogue of pyrrole:



which as I am sure everyone knows is called arsole.

Louis

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Louis



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(Permalink) Posted: May 17 2007,05:37   

Quote (Henry J @ May 17 2007,04:34)
Re "If you aren't part of the solution, you're part of the precipitate."

Well, at least we got that ironed out before the mixture of elements bonded to compound the problem.

Henry

{Argh, On a chemical pun cascade I see}

Unfortunately I don't have a suitable filter to prevent these boron puns. I'll stick a couple of burners under Dean, the developer, and his colleagues Lee and Bob, to make sure he, Lee....um....well, THEY sort it out. Anyway if Dean can pull this off then there is no doubt he will remind me that I owe Dean. Strange bloke Dean, obsessed with wild canids, sugar cane derived alcoholic beverages from Jamaica and playing the twiddly bits of guitar solos. He's always on about his wolf, rum and lead.

Enough of this nonsense. Back to combating creationism and its bastard offspring ID, which is after all nothing more than a silly con. Which cobalt together piece of antiscience will they provide us with next I wonder? Pity they're not anti money and political power otherwise we could have a rest. At least whatever they come out with we have a good retort.

Louis

P.S. How many shocking puns can you count in the above?

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Henry J



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(Permalink) Posted: May 17 2007,14:33   

Uh - I'm not sure what distinuishes shocking from non-shocking.

cascade
boron
burners (Bunsun?)
he, Lee....um
I owe Dean
wolf, rum
lead
cobalt

What with all those, I probably missed some.

Henry

  
MidnightVoice



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(Permalink) Posted: May 21 2007,10:24   

Quote (Louis @ May 17 2007,04:57)
I think the paper quoted (it's one of the Brown ones IIRC) refers not only to the antibodies we inherit via the placenta but (as Skeptic alludes to) the capabilities of our immune system to produce antibodies to threats we as individuals haven't encountered (perhaps yet) but we as an organism in a long chain of evolved organisms have. Meh, it probably needs rewording, cheers for pointing it out!



Louis

But the capability of our immunes system to produce antibodies that are specific is inherent in the DNA, and can provide an (estimated) 10 to the 11th different antibodies.  But these are nor specific to anything before they are made - the body ends up producing more of the ones that work.

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If I fly the coop some time
And take nothing but a grip
With the few good books that really count
It's a necessary trip

I'll be gone with the girl in the gold silk jacket
The girl with the pearl-driller's hands

  
Louis



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(Permalink) Posted: May 24 2007,03:56   

Quote
But the capability of our immunes system to produce antibodies that are specific is inherent in the DNA, and can provide an (estimated) 10 to the 11th different antibodies.  But these are nor specific to anything before they are made - the body ends up producing more of the ones that work.


To an extent this is why the analogy with bioactive secondary metabolites works, their formation is also encoded in the organisms DNA. The analogy isn't about which specific antibodies or metabolites are made but that for relatively little cost a very diverse set can be produced.

Anyway, what should be important about this bit of the OP is that it's about a lot of old crap! Hypothesis 2 for why some organisms produce secondary metabolites is very flawed (I mention this but probably needed to emphasise it more). The cost of some of these metabolites' production is not small and some of them are made in significant quantities, this breaks the analogy with the immune system used in hypothesis 2.  This is one of the reasons it's hypothesis 6 (along with proper hard evidence from the S coelicolor genome etc) that is currently most favoured. Obviously it's all a bit tentative (AFAIK), but based on the evidence we have it's the best explanation we have thus far.

Louis

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MidnightVoice



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(Permalink) Posted: May 25 2007,09:03   

Quote (Louis @ May 24 2007,03:56)
The cost of some of these metabolites' production is not small and some of them are made in significant quantities, this breaks the analogy with the immune system used in hypothesis 2.  
Louis

And the immune system responds mainly when it is needed (if it is working correctly), hence presumably saving energy.  I don't think that is the case with all secondary metabolites, but I am willing to be corrected  :)

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If I fly the coop some time
And take nothing but a grip
With the few good books that really count
It's a necessary trip

I'll be gone with the girl in the gold silk jacket
The girl with the pearl-driller's hands

  
Louis



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(Permalink) Posted: May 25 2007,10:13   

Quote
And the immune system responds mainly when it is needed (if it is working correctly), hence presumably saving energy.  I don't think that is the case with all secondary metabolites, but I am willing to be corrected


Well the microorganisms that make some of the most potent secondary metabolites do make more of them in more hostile surroundings (say a cubic centimetre of soil with lots of other microorganisms in).

The point of the analogy was diverse products for limited cost, one problem with it (amongst many!) is that the cost of some secondary metabolite production isn't so limited!

Louis

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Ichthyic



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(Permalink) Posted: May 25 2007,17:11   

Quote
Bioactive Secondary Metabolites In Nature


I was looking at the title again, thinking of exactly that (bioactive secondary metabolites) and was wondering if you've ever looked at DDE as a secondary metabolite of DDT?

I worked with a lab that was doing studies on the effects of DDE in marine mammals in CA back in the late 80's.

Nasty, and still showing signs of having severe adverse impacts to this day.

Not strictly related to the direction you are currently following, but I was just wondering if you'd ever glanced at the lit, or run across someone in your neck of the woods who had touched on it.

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"And the sea will grant each man new hope..."

-CC

  
qetzal



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(Permalink) Posted: May 25 2007,21:09   

Quote (Louis @ May 24 2007,03:56)
   
Quote
But the capability of our immunes system to produce antibodies that are specific is inherent in the DNA, and can provide an (estimated) 10 to the 11th different antibodies.  But these are nor specific to anything before they are made - the body ends up producing more of the ones that work.


To an extent this is why the analogy with bioactive secondary metabolites works, their formation is also encoded in the organisms DNA. The analogy isn't about which specific antibodies or metabolites are made but that for relatively little cost a very diverse set can be produced.

Louis, I'm curious. You're comparing diversity in secondary metabolites to diversity in antibodies.

With antibodies, there are mechanisms to generate diversity (e.g. VDJ recombination) plus mechanisms to preferentially amplify expression of "successful" antibodies (e.g. clonal expansion of B-cells).

Are there parallels to this for secondary metabolites? In other words, can some organisms preferentially select which metabolites to produce, depending on which one(s) will be most beneficial in a given setting?

  
Louis



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(Permalink) Posted: May 26 2007,05:34   

Quote
Are there parallels to this for secondary metabolites? In other words, can some organisms preferentially select which metabolites to produce, depending on which one(s) will be most beneficial in a given setting?


Well to be fair I'm not making the analogy I'm just reporting on one made in the lit, and it is not a good one I agree.

However back to the point!

The two things (secondary metabolism and the immune system) are not equivalent, and that isn't the point of the analogy. The point was that some organisms can produce a very diverse set of secondary metabolites that have different biological activities, and yes those organisms do sometimes produce different ratios of those secondary metabolites in different circumstances. Off the top of my head there are two main reasons this happens, different "foods" being consumed, and different "threats" being faced. So for example S. coelicolor produces different rations of secondary metabolites in a fungus dominated environment than in say a yeast dominated environment. So a very simplified answer to the question is "yes", but with some obvious reservations!

Obviously the analogy is going to be massively limited by the simple fact that immune systems are features of multicellular organisms and the ones I am discussing (mostly) here are unicellular, but the point wasn't about the similarity of their mechanisms or their nature, but the fact that (after the initial genetic investment, if you get my drift) that the cost of production of a diverse set of products (be they antibodies or metabolites) was relatively cheap.

Louis

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qetzal



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(Permalink) Posted: May 26 2007,09:22   

Quote (Louis @ May 26 2007,05:34)
[T]he point wasn't about the similarity of their mechanisms or their nature, but the fact that (after the initial genetic investment, if you get my drift) that the cost of production of a diverse set of products (be they antibodies or metabolites) was relatively cheap.

Louis

OK, but what makes the cost of secondary metabolites relatively cheap (at least, in the view of those who support that argument)?

I re-read your opening post, but it didn't seem very clear on this. At one point you mention high substrate tolerance in certain enzymes. Is the point that some individual enzymes can produce relatively diverse secondary metabolites by accepting a broader than normal range of substrates?

  
Louis



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(Permalink) Posted: May 26 2007,13:33   

Hi Qetzal,

Secondary metabolites AREN'T that cheap (it was a hypothesis people developed to explain things. Further research revealed it to be a poor hypothesis), which is why hypothesis 2 (or one reason why) falls down. As I said upthread to Midnight Voice, yup that bit of the OP needs a rewrite. I did point out early on it was a cut and paste cobbled together version of an old bit of thesis intro, not a perfect thing. Sorry for any confusion caused.

Quote
Is the point that some individual enzymes can produce relatively diverse secondary metabolites by accepting a broader than normal range of substrates?


Simple answer is : yes this is part of the point. As I said in the OP one of the problems with hypothesis 2 is that substrate tolerance is very variable across species and natural products. So basically hypothesis 2 might be true for some species and some natural products  i.e. in those species which have enzymes involved in primary metabolism which tolerate the substrate dependant chemistry used to make some secondary metabolites, or in which the secondary metabolites are "cheap" outgrowths of primary metabolism, but there's not sufficient evidence to support it in most species studied AFAIK.

Louis

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Louis



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(Permalink) Posted: July 20 2007,09:03   

Well today's reading has found this:

Nature Chemical Biology Focus on Natural Products

Access is free for July.

I thought these two PDFs of particular interest to AtBCers.

All Natural

One Pathway, Many Products

Louis

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Arden Chatfield



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(Permalink) Posted: July 20 2007,09:54   

Louis, none of this fancy educated-talk fools us. We found out you actually work in an adult book shop in London.

:angry:

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Louis



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(Permalink) Posted: July 20 2007,10:06   

I wouldn't call it "work", it's more of a calling.

Louis

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J-Dog



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(Permalink) Posted: July 20 2007,12:14   

Quote (Arden Chatfield @ July 20 2007,09:54)
Louis, none of this fancy educated-talk fools us. We found out you actually work in an adult book shop in London.

:angry:

Arden - I hate to sound pedantic like Heddle, BUT Louis posted a link to "All Natural", not "Au Natural" . :)

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Come on Tough Guy, do the little dance of ID impotence you do so well. - Louis to Joe G 2/10

Gullibility is not a virtue - Quidam on Dembski's belief in the Bible Code Faith Healers & ID 7/08

UD is an Unnatural Douchemagnet. - richardthughes 7/11

  
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