Streptomycete

Subsequently, other structural variations were reported encompassing compounds such as PS-5 (5) (5), carpetimycin A (6) (6), asparenomycin A (7) (7), and pluracidomycin A (8) (8), from a wide variety of streptomycete strains. Following these stmctures the simplest member of the series, having the completely unsubstituted nucleus, (1, X = CH2), was isolated from bacterial strains of Serratia and Ervinia (9). AH other natural products reported have substituents at both the C-6 and C-2 positions of the bicycHc ring system. Differences in the nature and stereochemistry of these substituents has provided a wide variety of stmctures, and over forty variations have been reported and comprehensively Hsted (10). 

Occurrence, Fermentation, and Biosynthesis. Although a large number of Streptomjces species have been shown to produce carbapenems, only S. cattkja (2) and S. penemfaciens (11) have been reported to give thienamycin (2). Generally the antibiotics occur as a mixture of analogues or isomers and are often co-produced with penicillin N and cephamycin C. Yields are low compared to other P-lactams produced by streptomycetes, and titres are of the order of 1—20 p-g sohdusmL despite, in many cases, a great deal of effort on the optimization of the media and fermentation conditions. The rather poor stabiUty of the compounds also contributes to a low recovery in the isolation procedures. The fermentation and isolation processes for thienamycin and the olivanic acids has been reviewed in some detail (12). 

Most peptide antibiotics have been isolated from Jictinomycetes and especially from Streptomjces. Many P-lactams, however, and a few other useful peptide antibiotics have come from fungi. These streptomycete and fungal peptide antibiotics include many stmctural types having varied therapeutic indications and/or scientific appHcations. 

Bleomycin and cyclosporine are the two economically most important streptomycete peptide antibiotics used as antitumor agents and immunomodulators, although dactinomycin is important medically for several tumors (see Chemotherapeutics, anticancer Immunotherapeutic agents). 

Ubenimex, [(2(3),3(R))-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine, was isolated as an inhibitor of aminopeptidases, on which it acts as a strong, reversible transition-state analogue inhibitor (293). Analogues of ubenimex have been made and some other aminopeptidase inhibitors, not all of them peptides, have been isolated from streptomycetes (294—296). 

Studies on marine micro-organisms, V. A new antibiotic, aplasmomy-cin, produced by a streptomycete isolated from shallow sea mud, Y. Okami, T. Okazaki, T. Kitahara, and H. Umezawa, J. Antibiot., 29 (1976) 1019-1025. 

From the cultures of streptomycetes were isolated anthacyclinones like aklavi-none. Various aromatic polyketide antibiotics produced by fungi and bacteria have quinoid structures, for example, doxorubicin, rhodomycin, and actinorhodin. ... 

Bentley, R. and Meganathan, R., Geosmin and methylisobomeol biosynthesis in Streptomycetes. FEES Lett., 25, 220, 1981. 

Chun, J. Ward, A. C. Kang, S. Hah, Y. C. Goodfellow, M. Long-term identification of Streptomycetes using pyrolysis mass spectrometry and artificial neural networks. Zbl. Bakt. 1997,185, 258-266. 

Secondary metabolites generated via the propionate route are quite unusual in nature. Relevant exceptions are some antibiotic macrolides from Streptomycetes [42], but wholly propionate-derived macrolides are rare. This biosynthetic pathway has been well proved for erythromycin (13), where the aglycone is produced by assembling seven propionate units [43, 44], and for a few related antibiotics [45]. However, very sophisticated biosynthetic experiments [46] have established that some apparent propionate units in other macrolides (e.g., aplasmomycin [46]) from Streptomycetes could be formed either by C-methylation through S-adenosylmethionine or from glycerol. 

Chaiet, L., and Wolf, F.J. (1964) The properties of streptavidin, a biotin-binding protein produced by Streptomycetes. Arch. Biochem. Biophys. 106, 1-5. 

From Streptomyces cirratus 248-Sq2, cirratiomycin A (133, R = iBu) has been obtained, and has been found to be active in vitro against a narrow range of Lactobacillus and some strains of Streptococcus [367]. In addition, the peptide antibiotic (132, R = Me) is also produced by this Streptomycete [367]. 

Isolated from Streptomycetes Antibacterial and antifungal amino 90... 

Bibb MJ. (2005) Regulation of secondary metabolism in streptomycetes. Curr Opin Microbiol 8 208-215. 

Vezina C, Kudelski A, Sehgal SN. (1975) Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J Antibiot 28 721-726. 

TABLE 2.5. Proteins Encoded in the Genomic Region Covering Part of the A/m-cluster of Streptomycetes bluensis ISP5564 (ATCC27420) (Accession Codes X78972, AF126354)... 

The gene clusters for SPC biosynthesis from two different streptomycete strains, S. netropis DSM 40093 (former flavopersicus ) and S. spectabilis ATCC 27465 (DSM 40512), have been reported (see Table 2.6 and Figure 2.2) also, a pathway suggesting the involvement of the Spc-gene products has been proposed recently. " Therefore, we here sketch only briefly the pathway design for the formation of SPC under use of the proposals of Altenbuchner and co-workers. ... 

Kodani S, SapT, a lanthionine-containing peptide involved in aerial hyphae formation in the streptomycetes, Mol Microbiol 58 1368—1380, 2005. 

Sphydrofuran is a structurally unique secondary metabolite produced by a variety of Streptomycetes strains. The first total synthesis of this compound was based in the use of RAMA to catalyze the aldol addition of chloroacetaldehyde with DHAP that provides two of the three chiral centers of the target molecule. The third quaternary center was introduced via a highly diastereoselective Grignard addition of allylmagnesium bromide (Scheme 4.17) [41]. 

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