Saturday, March 11, 2006

Discussion thread on molecules secreted by Streptomyces.

Image from here.

How to start this assignment?

Discuss the biological importance of specialised molecules secreted by Streptomyces avermitilis. Discuss their structure, mode of synthesis, possible biological roles and practical applications.
(This topic might interest people who are not specially interested in medicine, but who like practical topics like biochemical engineering, biotechnology, human welfare advances to benefit Africa, or even animal husbandry. Avermectins are used to treat animal and human parasite infections.)

The first step in tackling the assignment topic is to read what David Hopwood had to say in 2003:

The Streptomyces genome—be prepared!
David A. Hopwood
Selected quotes from Hopwood 2003:
The completion of the sequence of a second Streptomyces chromosome further establishes these soil-dwelling bacteria as nature's most prolific producers of potentially useful pharmaceuticals.

Streptomyces avermitilis became famous for producing the anti-parasitic agent avermectin, which is used to rid livestock of worm and insect infestations and to protect large numbers of people from river blindness in sub-Saharan Africa. Knowledge of the sequence of its genome, reported in this issue by Ikeda et al.1, should help in the development of higher yielding strains. However, the significance of the work goes far beyond such an objective.

In the context of biotechnology, the most interesting finding in the two Streptomyces genomes is the abundance of genes that would encode enzymes for secondary metabolism. Before the genome was sequenced, three antibiotics and a spore pigment were known to be encoded in the S. coelicolor genome, but the sequence revealed two dozen clusters, for pigments, complex lipids, signaling molecules, and iron-scavenging siderophores. In a preliminary report on the S. avermitilis genome before completion [Ref]7, 25 such clusters were described, and this number has increased to 30 in the complete sequence. Even more remarkable, nearly all the clusters probably encode different compounds in the two species, indicating the large number of pathways that await discovery in the Actinomycetes as a whole. In both species, a majority of the clusters lie in or near the arm regions, suggesting that their products are conditionally adaptive. Indeed, there is increasing evidence that the full capacity for secondary metabolite production in soil microorganisms is not expressed under typical conditions used for antibiotic screening in the laboratory but that particular compounds are made only in response to specific physical, chemical, or biological stresses (see Fig. 1).

A recent report by Zazopoulos et al.8 provides striking support for this view. These authors identified a cassette of five genes responsible for biosynthesis of the DNA-damaging warhead of the enediyne class of antibiotics, and detected it in 15% of a random collection of Streptomycetes. None at first made the predicted compounds, but all could be persuaded to do so under special fermentation conditions.
News and Views
Nature Biotechnology 21, 505 - 506 (2003)

Clearly there is a lot of choice as far as what Streptomycete molecules you can write about, because the message from David Hopwood's article is that Steptomycetes produce mumerous different compounds, and potentially produce compounds that have not yet even been detected directly. Thus there is good scope for discussing secreted molecules other than avermectins.

As far as their biological functions, there is a lot to be said too. Streptomycete "secondary metabolites" as they are called, are not just antibiotics.

One can even ask:

In what chemical languages do streptomycete cells communicate with one another to cooperate when they kill worms for food in the soil?

As a small (undersized for my age) boy I played rugby. (Rugby Union of course). With the right tackling technique and complete absence of fear, I could bring down the big boys by taking out the ankles of a runner. That's why I admire tiny Streptomyces avermitilis. It can take out the big guys like flatworms.

(Side note: rugby injuries put me in bed for about one month at age 11 years and I never played football again after that. However I have retained since then an obsessive fear of doctor's needles, which were used at that time to inject me intamuscularly with penicillin to combat the Clostridium bacteria that infected the injury, and whose neurotoxins made me delerious and accentuated my fear of needles.)


Anonymous Anonymous said...

Dear Microbe Pundit,
If I choose to write my assignment on quorum sensing in Streptomyces, can I use species other avermitilis as a basis? There seems to be more information quorum sensing in Sterptomyces natalensis

March 30, 2006 5:54 pm  
Blogger Microbe Pundit said...

Thats ok. You might like to point out how what you fing with S. natalensis could be relevant to future work with S avermitilis.

The idea of discussing the way in which QS signals are secreted and what they do is very good. I mentioned one pump that does this in class.

Which is it?
What organism?

As part of your essay try and sommarise what types of QS signals are generally used in Streptomyces- general concepts.

Good luck and post any questions you have here to share with others.

Most science networking is via computer so start getting practice now!

March 31, 2006 2:58 pm  
Anonymous Anonymous said...

Dear microbe pundit,

In provided assignment guide paper , you stated that our report need to contain sections included organism cell stucture, life cycle and biology. But if i choose Streptomyces avermilitis as topic, do i still need to write for all that above or i just focus on its secondary metabolites secretion, roles of functions and applicationS? Or do i need to include both?

In addition, may i know the difference between what to be included in introduction and literature review?

Thanks a lot!

March 31, 2006 9:45 pm  
Blogger Microbe Pundit said...

I think you should use the guidlines intelligently for your topic.

Also understanding of the natural functions and biological role of your secreted compound is highly valued.

The secreted compound very likely have roles connected with cell differention, regulation and communication. Consider these things in writing your assignment.

As far as the review and introduction, the review of the literature that you carry out will be useful for writing your entire essay. Exactly what you put in your introduction, and what elswhere depends on what you find and the way in which you develop your them.

The guidelines are suggestion to get you moving in the right direction.

Whatever goes, logical clarity and development of biologically useful concepts is important.

April 01, 2006 2:03 pm  
Anonymous Anonymous said...

hi...when you say discuss their you mean:
1) the genome structure of s.avermitilis?
2)the structure of the specialised molecules secreted by s. avermitilis?
3) the physical structure of s. avermitilis?

April 18, 2006 11:19 pm  
Anonymous Anonymous said...

can you explain in more details by "mode of synthesis"

April 19, 2006 1:32 am  
Blogger Microbe Pundit said...

Re: Structure: The natural aspect of structure to focus on is structure of the secreted molecules, and possibly the pats of the transport systems involved in secretion.

This question suggests you are focusing to much on what I say rather than thinking about the topic. The major function odf the assignment is to get you thinking analytically about the assigned theme.

RE: mode of synthesis, this means the chemical processes used to make the compounds in question.

May 02, 2006 1:11 pm  

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