Streptomyces species

Fosfomycin is an antibiotic produced by several Streptomyces species [95, 96] as well as by the Gram-negative Pseudomonas syringiae and Pseudomonas viridiflava. dl, 98] As an analogue of phosphoenolpyruvate, it irreversibly inhibits UDP-N-acetylglu-cosamine-3-O-enolpymvyltransferase (MurA), the enzyme that catalyzes the first step in peptidoglycan biosynthesis [99]. 

One example of a naturally occurring diazirine, duazomycin A (137 Scheme 11.20), has been reported, isolated in 1985 from a Streptomyces species during a screen for herbicidal compounds [196], It was fotind to inhibit de novo starch synthesis and it was suggested that this is due to direct inhibition of protein synthesis. Duazomycin A is structurally related to 6-diazo-5-oxo-L-norleucine (138), also reported as a natural product from Streptomyces [197], which acts as a glutamine antagonist and inhibits purine biosynthesis [198],... 

Phenazines — This large class of compounds includes more than 6,000 natural and synthetic representatives. Natural phenazines are secondary metabolites of certain soil and marine microorganisms. The main phenazine producers are Pseudomonas and Streptomyces species. Pseudomonas strains produce the most simple phenazines tubermycin B (phenazine-1-carboxylic acid), chlororaphine, pyocyanin, and iodinine. Pyocyanin is a blue pigment while chlororaphine is green both are produced by Pseudomonas aeruginosa. They can be seen in infected wounds of animal and human skins. Iodinine is a purple phenazine produced by Pseudomonas aureofaciens. 

Kamel, Z., Toxicity of cadmium to two Streptomyces species as affected by clay minerals, Plant Soil, 93 (2), 195-203, 1986. 

The carbinolamine-containing pyrrolo[2,l-c][l,4]benzodiazepine family of antitumor antibiotics is produced by various Streptomyces species well-known members include abthramy-cine, tomay mycine, and DC-81,138 Various approaches to the synthesis of these compounds have been investigated over past years reductive cyclization of suitably substituted nitroaldehydes is the frequently used method (Eq. 10.81).139... 

Saimura M, Takehara M, Mizukami S et al (2008) Biosynthesis of nearly monodispersed poly (s-L-lysine) in Streptomyces species. Biotechnol Lett 30 377-385... 

The degradation of azo dyes in aerobiosis can also be carried out by lignindegrading fungi, mainly white-rot fungi, or by peroxidase-producing bacterial strain, mainly Streptomyces species, as extensively reviewed by Stolz [4]. 

Phencomycin (57) was recovered from Streptomyces sp HIT Y-9031725 [58]. A natural product that is structurally very similar was discovered by Laatsch et al. in a marine Streptomyces species, interestingly in its reduced form, i.e., the dihydrophencomycin methyl ester (58) [59]. Both show weak antibiotic activity. 

First among the aminoglycosides was streptomycin, one of several antibiotics isolated from Streptomyces species by Selman Waksman—this from S. griseus in 1944. Waksman proved to be an enormously effective seeker of antibiotics in natural products. In addition to streptomycin, he discovered neomycin, another widely used antibiotic. Less important discoveries include actinomycin, clavacin, streptothricin, grisein, fradicin, and candidin. Waksman received the Nobel Prize in Physiology or Medicine in 1952. 

Perhaps a bit more subtle than those agents that react chemically with DNA are those that insert themselves between the stacked bases of the DNA double helix— intercalation. This alters the regular structure of the DNA molecule and may lead, for instance, to inhibition of mRNA synthesis. The structures of the intercalcating agents are generally quite complex and I will spare you the complexity. However, three names may be familiar—dactinomycin (Actinomycin D), daunorubicin (daunomycin), and doxorubicin (Adriamycin)— and intercalation is how they work. All three are natural products and were isolated from the fermentation broths of Streptomyces species. 

Note on spelling -mycin designates origin from Streptomyces species -mi-cin (e.g., gentamicin) from Micromonospora species. 

Gindamydn has antibacterial activity similar to that of erythromycin. It exerts a bacteriostatic effect mainly on gram-positive aerobic, as well as on anaerobic pathogens. Gindamycin is a semisynthetic chloro analogue of lin-comycin, which derives from a Streptomyces species. Taken orally, clindamycin is better absorbed than lincomycin, has greater antibacterial efficacy and is thus preferred. Both penetrate well into bone tissue. 

Tacrolimus, a macrolide, derives from a streptomyces species pharmacologically it resembles cyclosporin A, but is more potent and efficacious. 

Antibiotic production and morphological differentiation (formation of aerial mycelium and sporulation) in Streptomyces species and in some other actinomycetes is regulated by small signaling molecules called y-butyrolactones or butanolids. These quorum-sensing signals bind to... 

Macrolides, lincosamides and streptogramins are protein biosynthesis inhibitors that bind to 50S subunit of the ribosome and inhibit peptidyl tRNA translocation from the A-site to the P-site." Macrolides have a glycosylated 14-, 15- or 16-membered lactone ring structure and are produced by several species of Streptomyces. Lincosamide antibiotics were isolated initially from Streptomyces lincolnensis but later isolated from different species of Streptomcyces. Streptogramins were also isolated from Streptomycesgraminofaciens and subsequently from several different Streptomyces species. There are two structurally different streptogramins, A and B they are bacteriostatic individually and can be bactericidal when combined. 

Novobiocin (Fig. 8) is a glycosidic antibiotic isolated from Streptomyces species.Its mode of action was identified by Smith as DNA biosynthesis inhibitor and it was found to target the B subunit of DNA Gyrase, a DNA replication enzyme (Fig. 1). 

The involvement of isobutylhydroxylamine, (CH3)2CHCH2NH—OH (4), and of HA (NH2OH) in the biosynthesis of the antibiotics valanimycin (5) and nebularine (6), respectively, has been demonstrated in Streptomyces species (see Section n.B). In the case of nebularine, HA is released in the final step of its production by enzymatically induced deamination of adenosine, while the isobutylhydroxylamine is a precursor for the biosynthesis of valanimycin. In cyanobacterium, the presence of free and bound HA was demonstrated to be a product of enzyme-mediated glutamine oxidation ... 

Production of HA during the biosynthesis of the antibiotic nebularine (6) was demonstrated in another Streptomyces species. The formation of HA was confirmed both by chemical reactions designed to detect it and by MS analysis. An unusual enzymic deamination of adenosine was suggested, which resulted in release of HA, rather than of NH3, as a key step in the production of nebularine (equation 6). 

A broad range of structurally diverse 3,4-dioxygenated carbazole alkaloids, such as the carbazomycins A-F (260-265) and the neocarazostatins A-C (266-268) were isolated from different Streptomyces species. 

In the past decade, Seto et al. reported the isolation of a series of unprecedented carbazoIe-3,4-quinone alkaloids from various Streptomyces species. In 1993, the first example of a carbazole-3,4-quinone alkaloid, carquinostatin A (278) was isolated... 

The fermentation broth of various Streptomyces species can be separated into an acidic fraction shown to contain pentalenic acid 776) The somewhat less oxidized pentalenolactone precursor has been independently prepared from humulene from which is is probably derived biogenetically Thus, treatment of humulene with mercuric nitrate followed by aqueous potassium bromide solution gave two bromo-mercury derivatives which were oxygenated in the presence of sodium borohydride. The resulting pair of diols (770 and 771) were separately converted to exo methylene... 

The first antitumor antibiotic was actinomycin A which was isolated from a Streptomyces species. The actinomycins are chromopeptides containing a planar chromophore, responsible for the bright color of the compounds, with peptide side chains. The most important representative of this group which is in clinical use is actinomycin D, or dactinomycin. 

The metabolic functionalization of cannabinoids is of continuing interest (c/. Vol. 4, p. 71 Vol. 7, p. 50). A -THC may be hydroxylated at C-4 using Mycobacterium rhodochrous (together with aromatization) or at C-4" of the side-chain with Bacillus cereus or may be oxygenated at C-5 with Streptomyces species. A -THC has been hydroxylated in both the ring system and the side-chain with Pellicularia filamentosa and Streptomyces lavendulae, and further evidence in favour of in vivo epoxy metabolites and derivatives in the mouse has been presented (cf. Vol. 4,... 

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