Streptomyces metabolites

Some of these compounds could be considered as dietary additives, but various other terms, including pesticides, can also be used. They can have beneficial effects on the environment and this aspect will be discussed later. The ionophore monensin, which is an alicyclic polyether (Figure 1), is a secondary metabolite of Streptomyces and aids the prevention of coccidiosis in poultry. Monensin is used as a growth promoter in cattle and also to decrease methane production, but it is toxic to equine animals. " Its ability to act as an ionophore is dependent on its cyclic chelating effect on metal ions. ° The hormones bovine somatotropin (BST) and porcine somatotropin (PST), both of which are polypeptides, occur naturally in lactating cattle and pigs, respectively, but can also be produced synthetically using recombinant DNA methods and administered to such animals in order to increase milk yields and lean meat production. "... 

S,3S)-(+)-Aziridine-2,3-dicarboxylic acid (234 Scheme 3.86), an example of a naturally occurring aziridinecarboxylic acid, is a metabolite of Streptomyces MD398-A1. This aziridine was prepared by treatment of diethyl (2i ,3K)-(-)-oxir-ane-2,3-dicarboxylate (231) with trimethylsilyl azide in EtOH/DMF to produced azido alcohol 232 [137], and treatment of this alcohol with triphenylphosphine afforded the aziridine dicarboxylate 233 in 71 % yield. Hydrolysis of 233 afforded the natural product 234 in 69% yield. 

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. 

Reid KA, JTG Hamilton, RD Bowden, D O Hagan, L Dasaradhi, MR Amin, DB Harper (1995) Biosynthesis of fluorinated seeondary metabolites by Streptomyces cattleya. Microbiology (UK) 141 1385-1393. 

Abel, C.B.L., Lindon, J.C., Noble, D., Rudd, B.A.M., Sidebottom, P.J., and Nicholson, J.K, Characterization of metabolites in intact Streptomyces citricolor culture supernatants using high-resolution nuclear magnetic resonance and directly coupled high-pressure liquid chromatography-nuclear magnetic resonance spectroscopy, Anal. Biochem., 270, 220, 1999. 

Streptomyces strains are Gram positive [54], they have good secretion capacities and extensive fermentation knowledge has been accumulated. Mostly, they were used for the production of secondary metabolites with potent biological activities, such as antibiotics, immunosuppressors or pesticides. Constitutive [55] and inducible [56] expression is possible. Up to 40% of the total soluble cellular protein was reported in the case of inducible expression. 

Highly active super strains, such as Cunninghamella sp., Beauveria bassiana and Streptomyces rimosus, are particularly useful here, as they tend to produce multiple metabolites thus, the majority of the desired metabolites can be obtained with a minimal number of incubations. 

Canned, R.J., Knaggs, A.R., Dawson, M.J. et al. (1995) Microbial biotransformation of the angiotensin II antagonist GR117289 by Streptomyces rimosus to identify a mammalian metabolite. Drug Metabolism and Disposition The Biological Fate of Chemicals, 23, 724—729. 

Cannel, R.J.P., Rashid, T., Ismail, I.N. et al. (1997) Novel metabolites of warfarin produced by Beauveria bassiana and Streptomyces rimosus a novel application of HPLC-NMR. Xenobiotica The Fate of Foreign Compounds in Biological Systems, 27, 147-157. 

Figure 11.1 Representative secondary metabolites produced by Streptomyces ceolicolor and other microorganisms, including aromatic polyketides actinorhodin and tetrohydroxynaphthalene (a), side-rophore desferrioxamines (b), polyunsaturated fatty acid eicosapentaenoic acid (c) and terpenoids beta-...

Tahlan, K., Park, H.U., Wong, A., Beatty, P.H. and Jensen, S.E. (2004) Two sets of paralogous genes encode the enzymes involved in the early stages of clavulanic acid and clavam metabolite biosynthesis in streptomyces clavuligenis. 48, 930-939. 

The final stages of the synthesis of (—)-A-58365B, a Streptomyces metabolite that inhibits the angiotensin-converting enzyme, involve several reactions at substituents attached to ring carbon atoms of a quinolizidine system. Thus, ozonolysis of the exocyclic methylene side chain of compound 107, followed by base-induced elimination and carboxyl deprotection, gave 108 (Scheme 12) <1999JOC1447>. 

Hufford et al [57] used proton and 13C NMR spectrometric data to establish the novel sulfur-containing microbial metabolite of primaquine. Microbial metabolic studies of primaquine using Streptomyces roseochromogenus produced an A-acety-lated metabolite and a methylene-linked dimeric product, both of which have been previously reported, and a novel sulfur-containing microbial metabolite. The structure of the metabolite as an S-linked dimer was proposed on the basis of spectral and chemical data. The molecular formula C34H44N604S was established from field-desorption mass spectroscopy and analytical data. The 1H- and 13C NMR spectra data established that the novel metabolite was a symmetrical substituted dimer of primaquine A-acetate with a sulfur atom linking the two units at carbon 5. The metabolite is a mixture of stereoisomers, which can equilibrate in solution. This observation was confirmed by microbial synthesis of the metabolite from optically active primaquine. 

When (V-acetylprimaquine (175) was incubated for prolonged periods of time with Candida tropicalis (ATCC 20021) (232) and Streptomyces rimosus (ATCC 23955) (233), two unusual minor dimeric metabolites were obtained. These were identified as the methylene-linked compound 177 formed by C. tropicalis and the biaryl-linked compound 178 formed by 5. rimosus. Both dimeric metabolites were prepared synthetically to confirm their identities. 

Fig. 10.7. Inh ibitor binding to individual active sites of the yeast 20S proteasome. The inhibitors lactacystin (A), epoxomicin (B) and TMC95A (C) are colored green and are shown in stereo mode together with their unbiased electron densities. The active-site Thrl is highlighted in black. (A) Covalent binding of the Streptomyces metabolite lactacystin to the active site of 5. The SI pockets of the active subunits and differ from that of 5 and are not suitably constructed to bind the inhibitor. As discussed in the text, Met45 (black), which is located at the bottom of the 5-Sl pocket, makes the difference for inhibitor...

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