New Insights into Chloramphenicol Biosynthesis in Streptomyces venezuelae ATCC 10712

L. T. Fernandez-Martinez, C. Borsetto, J. P. Gomez-Escribano, M. J. Bibb, M. M. Al-Bassam, G. Chandra, M. J. Bibb

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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.
Original languageEnglish
Pages (from-to)7441-7450
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume58
Issue number12
Early online date29 Sep 2014
DOIs
Publication statusPublished - 1 Dec 2014

Keywords

  • Acyl Carrier Protein/genetics
  • Bacterial Proteins/genetics
  • Chloramphenicol/biosynthesis
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial
  • Metabolic Networks and Pathways/genetics
  • Microarray Analysis
  • Molecular Sequence Annotation
  • Multigene Family
  • Mutation
  • Sequence Analysis, DNA
  • Sodium-Hydrogen Exchangers/genetics
  • Streptomyces/genetics
  • Transcription Factors/genetics
  • Transcription, Genetic
  • Transferases (Other Substituted Phosphate Groups)/genetics

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    Dr LORENA FERNANDEZ-MARTINEZ

    • Biology - Reader in Microbial Genetics

    Person: Academic

    Cite this

    Fernandez-Martinez, L. T., Borsetto, C., Gomez-Escribano, J. P., Bibb, M. J., Al-Bassam, M. M., Chandra, G., & Bibb, M. J. (2014). New Insights into Chloramphenicol Biosynthesis in Streptomyces venezuelae ATCC 10712. Antimicrobial Agents and Chemotherapy, 58(12), 7441-7450. https://doi.org/10.1128/AAC.04272-14