Generation of novel pikromycin antibiotic products through mutasynthesis

Shuchi Gupta, Venkatraman Lakshmanan, Beom Seok Kim, Robert Fecik, Kevin A. Reynolds

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The pikromycin polyketide synthase (PKS) of S. venezuelae, which consists of one loading module and six extension modules, is responsible for the formation of the hexaketide narbonolide, a key intermediate in the biosynthesis of the antibiotic pikromycin. S. venezuelae strains in which PikAI, which houses the loading domain and first two modules of the PKS, is either absent or catalytically inactive, produce no pikromycin product. When these strains are grown in the presence of a synthetically prepared triketide product, activated as the N-acetylcysteamine thioester, pikromycin yields are restored to as much as 11% of that seen in the wild-type strain. Feeding analogues of the triketide intermediate provides pikromycin analogues bearing different alkyl substituents at C13 and C14. One of these analogues, Δ15,16-dehydropikromycin, exhibits improved antimicrobial activity relative to pikromycin.

Original languageEnglish
Pages (from-to)1609-1616
Number of pages8
JournalChemBioChem
Volume9
Issue number10
DOIs
Publication statusPublished - 2008 Jul 2

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Anti-Bacterial Agents
Polyketide Synthases
Bearings (structural)
Biosynthesis
picromycin

Keywords

  • Biosynthesis
  • Natural products
  • Pikromycin
  • Polyketides
  • Triketides

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Medicine(all)

Cite this

Generation of novel pikromycin antibiotic products through mutasynthesis. / Gupta, Shuchi; Lakshmanan, Venkatraman; Kim, Beom Seok; Fecik, Robert; Reynolds, Kevin A.

In: ChemBioChem, Vol. 9, No. 10, 02.07.2008, p. 1609-1616.

Research output: Contribution to journalArticle

Gupta, S, Lakshmanan, V, Kim, BS, Fecik, R & Reynolds, KA 2008, 'Generation of novel pikromycin antibiotic products through mutasynthesis', ChemBioChem, vol. 9, no. 10, pp. 1609-1616. https://doi.org/10.1002/cbic.200700635
Gupta, Shuchi ; Lakshmanan, Venkatraman ; Kim, Beom Seok ; Fecik, Robert ; Reynolds, Kevin A. / Generation of novel pikromycin antibiotic products through mutasynthesis. In: ChemBioChem. 2008 ; Vol. 9, No. 10. pp. 1609-1616.
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