Streptomyces - Genus of plenty (of drugs)

Okay. Actinomycetes are a group (phyla, actually) of Gram-positive bacteria that like hanging out in soil and water (as decomposers of organic materials) and plants and animals (some are pathogenic, while others do the whole symbiotic thing). The Actinomycetes get their name from the fact that some of them form branching filaments that look kind of like the branching hyphae (collectively referred to as a mycelium) formed by fungi. In an effort to lessen confusion, Actinomycetes are now commonly referred to as Actinobacteria.

Actinobacteria are neat because they tend to produce cool secondary metabolites, many of which have been successfully isolated and turned into useful drugs and other organic chemicals. In particular, an appreciable number of Actinobacteria produce antibiotics, which they use to compete with fungi and other bacteria for resources (and because they are totally badass). The genus Streptomyces (not to be confused with Streptococcus!) is a particularly fruitful source of these compounds, a number of which have been developed as antifungals, antibiotics (antibacterials), and chemotherapeutic (anticancer) drugs. Sit tight, here we go with the lists.

Streptomyces-derived antifungals tend to be macrolide polyenes (large ring structure with lots of conjugated carbon-carbon double bonds), and include such illustrious members as: nystatin (the first Actinobacteria-sourced human antifungal, made by S. noursei), amphotericin B (made by S. nodosus, originally isolated from a sample of Venezuelan soil), and natamycin (made by S. natalensis, insert not-a-mycin joke here).

There are a friggin’ tonne of Streptomyces-derived antibiotics used specifically as antibacterial agents. To begin with, a good number of the aminoglycosides (a class of antibiotics that possess cyclohexyl rings substituted with amine groups and linked together by glycosidic bonds) are the work of this genus. These include: streptomycin (S. griseus), neomycin (S. fradiae), and kanamycin (S. kanamyceticus).

Other antibacterial antibiotics of note include: erythromycin (a macrolide that often subs for penicillin when people be allergic to it, made by S. erythraea), tetracycline (a longstanding acne drug that makes you light-sensitive, made by S. rimosus), chloramphenicol (cheap, effective, but can cause aplastic anemia, made by S. venezuelae), vancomycin (a relatively ginormous glycopeptide that can turn people red, made by S. orientalis), and thienamycin (made by S. cattleya, modified by us to make imipenem, the first carbapenem beta-lactam antibiotic). Whew!

Here is where it gets really cool. A number of the antibiotics produced by Streptomyces have proven to be too toxic for use as antibiotics in humans, but because of their toxicity towards cells (specifically dividing cells) they have been reinvented as chemotherapy drugs. We’re talking drugs like: actinomycin-D (the original), bleomycin (glycopeptide made by S. verticullus), mitomycin (aziridine made by S. lavendulae), and plicamycin (made by S. plicatus). Plus we have the anthracyclines daunorubicin and doxorubicin (S. peucetius), and migrastatin (macrolide, under investigation, made by S. platensis).

Whoo-wee! As you may have noticed, drugs isolated from species of Streptomyces tend to have the suffix -mycin, although there are lots of exceptions. And that's that.

- Birnbaum J, Kahan FM, Kropp H, MacDonald JS (1985). Carbapenems, a new class of beta-lactam antibiotics. Discovery and development of imipenem/cilastatin. Am. J. Med. 78 (6A): 3-21.
- http://en.wikipedia.org/wiki/Actinobacteria
- http://en.wikipedia.org/wiki/Streptomyces

2 chemically inspired comments:

César Sánchez said...

Very nice post, Chris!

(Sorry I'm not very (chemically) inspired, but really enjoyed your post!)

Chris said...

No worries, César. I like your blog!