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.)