Journal of Industrial Microbiology and Biotechnology

, Volume 33, Issue 2, pp 121–128

Heterologous production of daptomycin in Streptomyces lividans

  • Julia Penn
  • Xiang Li
  • Andrew Whiting
  • Mohammed Latif
  • Trevor Gibson
  • Christopher J. Silva
  • Paul Brian
  • Julian Davies
  • Vivian Miao
  • Stephen K. Wrigley
  • Richard H. Baltz
Original Paper

DOI: 10.1007/s10295-005-0033-8

Cite this article as:
Penn, J., Li, X., Whiting, A. et al. J IND MICROBIOL BIOTECHNOL (2006) 33: 121. doi:10.1007/s10295-005-0033-8

Abstract

Daptomycin and the A21978C antibiotic complex are lipopeptides produced by Streptomyces roseosporus and also in recombinant Streptomyces lividans TK23 and TK64 strains, when a 128 kbp region of cloned S. roseosporus DNA containing the daptomycin gene cluster is inserted site-specifically in the ϕC31 attB site. A21978C fermentation yields were initially much lower in S. lividans than in S. roseosporus, and detection was complicated by the production of host metabolites. However A21978C production in S. lividans was improved by deletion of genes encoding the production of actinorhodin and by medium optimization to control the chemical form of the calcium dependent antibiotic (CDA). This latter compound has not previously been chemically characterized as a S. lividans product. Adding phosphate to a defined fermentation medium resulted in formation of only the phosphorylated forms of CDA, which were well separated from A21978C on chromatographic analysis. Adjusting the level of phosphate in the medium led to an improvement in A21978C yield from 20 to 55 mg/l.

Keywords

DaptomycinA21978CCalcium-dependent antibiotic (CDA)ActinorhodinStreptomyces lividans

Copyright information

© Society for Industrial Microbiology 2005

Authors and Affiliations

  • Julia Penn
    • 1
  • Xiang Li
    • 2
  • Andrew Whiting
    • 1
  • Mohammed Latif
    • 1
  • Trevor Gibson
    • 1
  • Christopher J. Silva
    • 2
  • Paul Brian
    • 2
  • Julian Davies
    • 2
    • 3
  • Vivian Miao
    • 2
  • Stephen K. Wrigley
    • 1
  • Richard H. Baltz
    • 2
  1. 1.Cubist Pharmaceuticals (UK) LtdSloughUK
  2. 2.Cubist Pharmaceuticals, IncLexingtonUSA
  3. 3.Dept of Microbiology and ImmunologyUniversity of British ColumbiaVancouverCanada