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Titolo:
HYDROXYLATION OF MACROLACTONES YC-17 AND NARBOMYCIN IS MEDIATED BY THE PIKC-ENCODED CYTOCHROME-P450 IN STREPTOMYCES-VENEZUELAE
Autore:
XUE YQ; WILSON D; ZHAO LS; LIU HW; SHERMAN DH;
Indirizzi:
UNIV MINNESOTA,DEPT MICROBIOL 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:
Chemistry & biology
fascicolo: 11, volume: 5, anno: 1998,
pagine: 661 - 667
SICI:
1074-5521(1998)5:11<661:HOMYAN>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
NUCLEOTIDE-SEQUENCE ANALYSIS; BIOSYNTHETIC GENE-CLUSTER; SACCHAROPOLYSPORA-ERYTHRAEA; ERYTHROMYCIN BIOSYNTHESIS; ESCHERICHIA-COLI; 6-DEOXYERYTHRONOLIDE-B HYDROXYLASE; IDENTIFICATION; EXPRESSION; RAPAMYCIN; CLONING;
Keywords:
CYTOCHROME P450; MACROLIDE ANTIBIOTICS; NARBOMYCIN; POLYKETIDE SYNTHASE; YC-17;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
24
Recensione:
Indirizzi per estratti:
Citazione:
Y.Q. Xue et al., "HYDROXYLATION OF MACROLACTONES YC-17 AND NARBOMYCIN IS MEDIATED BY THE PIKC-ENCODED CYTOCHROME-P450 IN STREPTOMYCES-VENEZUELAE", Chemistry & biology, 5(11), 1998, pp. 661-667

Abstract

Background: Streptomyces venezuelae produces two groups of antibiotics that include the 12-membered ring macrolides methymycin and neomethymycin, and the 14-membered ring macrolide pikromycin. Methymycin and pikromycin are derived from the corresponding precursors, YC-17 and narbomycin, respectively, by hydroxylation of the tertiary carbon position (C-10 in YC-17 or C-12 in narbomycin) on the macrolactone ring. In contrast, neomethymycin is derived from YC-17 by hydroxylation of the secondary carbon (C-12) of the propionyl starter unit sidechain. Results: Using a genetic and biochemical approach we have characterized a single P450 hydroxylase (PikC) in the methymycin/pikromycin biosyntheticgene cluster (pik) from S. venezuelae. Inactivation of pikC abolishedproduction of all hydroxylated macrolides, with corresponding accumulation of YC-17 and narbomycin in the culture medium. The enzyme was produced efficiently and purified as a His-tagged protein from recombinant Escherichia coil cells. Purified PikC effectively converts YC-17 into methymycin and neomethymycin and narbomycin into pikromycin in vitro. Conclusions: These results demonstrate that PikC is responsible forthe conversion of YC-17 to methymycin and neomethymycin, and narbomycin to pikromycin in S. venezuelae. This substrate flexibility is unique and represents the first example of a P450 hydroxylase that can accept 12- and 14-membered ring macrolides as substrates, as well as functionalize at two positions on the macrolactone system. The broad substrate specificity of PikC provides a potentially valuable entry into theconstruction of novel macrolide- and ketolide-based antibiotics.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/12/20 alle ore 12:38:07