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New insights into chloramphenicol biosynthesis in Streptomyces venezuelae ATCC 10712.

Authors
  • Fernández-Martínez, Lorena T
  • Borsetto, Chiara
  • Gomez-Escribano, Juan Pablo
  • Bibb, Maureen J
  • Al-Bassam, Mahmoud M
  • Chandra, Govind
  • Bibb, Mervyn J
Type
Published Article
Journal
Antimicrobial Agents and Chemotherapy
Publisher
American Society for Microbiology
Publication Date
Dec 01, 2014
Volume
58
Issue
12
Pages
7441–7450
Identifiers
DOI: 10.1128/AAC.04272-14
PMID: 25267678
Source
Medline
License
Unknown

Abstract

Comparative genome analysis revealed seven uncharacterized genes, sven0909 to sven0915, adjacent to the previously identified chloramphenicol biosynthetic gene cluster (sven0916-sven0928) of Streptomyces venezuelae strain ATCC 10712 that was absent in a closely related Streptomyces strain that does not produce chloramphenicol. Transcriptional analysis suggested that three of these genes might be involved in chloramphenicol production, a prediction confirmed by the construction of deletion mutants. These three genes encode a cluster-associated transcriptional activator (Sven0913), a phosphopantetheinyl transferase (Sven0914), and a Na(+)/H(+) antiporter (Sven0915). Bioinformatic analysis also revealed the presence of a previously undetected gene, sven0925, embedded within the chloramphenicol biosynthetic gene cluster that appears to encode an acyl carrier protein, bringing the number of new genes likely to be involved in chloramphenicol production to four. Microarray experiments and synteny comparisons also suggest that sven0929 is part of the biosynthetic gene cluster. This has allowed us to propose an updated and revised version of the chloramphenicol biosynthetic pathway.

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