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Titolo:
A GENE-CLUSTER FOR MACROLIDE ANTIBIOTIC BIOSYNTHESIS IN STREPTOMYCES-VENEZUELAE - ARCHITECTURE OF METABOLIC DIVERSITY
Autore:
XUE YQ; ZHAO LS; LIU HW; SHERMAN DH;
Indirizzi:
UNIV MINNESOTA,DEPT MICROBIOL,BOX 196,1460 MAYO MEM BLDG MINNEAPOLIS MN 55455 UNIV MINNESOTA,DEPT MICROBIOL MINNEAPOLIS MN 55455 UNIV MINNESOTA,BIOL PROC TECHNOL INST MINNEAPOLIS MN 55455 UNIV MINNESOTA,DEPT CHEM MINNEAPOLIS MN 55455
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 21, volume: 95, anno: 1998,
pagine: 12111 - 12116
SICI:
0027-8424(1998)95:21<12111:AGFMAB>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
MODULAR POLYKETIDE SYNTHASE; SACCHAROPOLYSPORA-ERYTHRAEA; ERYTHROMYCIN BIOSYNTHESIS; ENZYMATIC DOMAINS; ESCHERICHIA-COLI; ORGANIZATION; CLONING; RAPAMYCIN; IDENTIFICATION;
Keywords:
POLYKETIDES; DEOXYSUGAR; KETOLIDE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
30
Recensione:
Indirizzi per estratti:
Citazione:
Y.Q. Xue et al., "A GENE-CLUSTER FOR MACROLIDE ANTIBIOTIC BIOSYNTHESIS IN STREPTOMYCES-VENEZUELAE - ARCHITECTURE OF METABOLIC DIVERSITY", Proceedings of the National Academy of Sciences of the United Statesof America, 95(21), 1998, pp. 12111-12116

Abstract

In a survey of microbial systems capable of generating unusual metabolite structural variability, Streptomyces venezuelae ATCC 15439 is notable in its ability to produce two distinct groups of macrolide antibiotics. Methymycin and neomethymycin are derived from the 12-membered ring macrolactone 10-deoxymethynolide, whereas narbomycin and pikromycin are derived from the 14-membered ring macrolactone, narbonolide. This report describes the cloning and characterization of the biosynthetic gene cluster for these antibiotics. Central to the cluster is a polyketide synthase locus (pikA) that encodes a six-module system comprised of four multifunctional proteins, in addition to a type II thioesterase (TEII), Immediately downstream is a set of genes for desosamine biosynthesis (des) and macrolide ring hydroxylation, The study suggests that Pik TEII plays a role in forming a metabolic branch through whichpolyketides of different chain length are generated, and the glycosyltransferase (encoded by desVII) has the ability to catalyze glycosylation of both the 12- and 14-membered ring macrolactones. Moreover, thepikC-encoded P450 hydroxylase provides yet another layer of structural variability by introducing regiochemical diversity into the macrolide ring systems. The data support the notion that the architecture of the pik gene cluster as well as the unusual substrate specificity of particular enzymes contributes to its ability to generate four macrolideantibiotics.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 02:04:23