Enhancement of pradimicin production in Actinomadura hibisca P157-2 by metabolic engineering

Sarita Paudel, Hei Chan Lee, Beom Seok Kim, Jae Kyung Sohng

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Actinomadura hibisca P157-2 produces potent antifungal antibiotic pradimicins. To enhance pradimicin production, ACCase from Streptomyces coelicolor and two regulatory genes metK1-sp and afsR-sp from Streptomyces peuticus were overexpressed into A. hibisca using an integration vector pSET152 under the control of the strong ermE promoter. The constructed plasmids pACC152, pSAM152, pAFS152, pSA152 and pASA152 were transformed into A. hibisca by the conjugal method. The recombinant strains A. hibisca ACC, A. hibisca SAM, A. hibisca AFS, A. hibisca SA and A. hibisca ASA produced greater amounts of pradimicin than the parental strain with an increment of 3-fold, 2.1-fold, 2.8-fold, 3.4-fold, and 4.5-fold respectively. To increase the acetyl-coA pool, the strains were fed methyl oleate and acetate as carbon sources. The production was increased in wild-type A. hibisca, A. hibisca ACC and A. hibisca ASA by 2.2-fold, 4.12-fold and 5.98-fold respectively, with oleate and by 1.12-fold, 3.8-fold and 5.38-fold respectively with acetate. The strain A. hibisca ASA remained the best strain for the production of pradimicin. The higher transcriptional levels of structural genes in the strains harboring metK1-sp and afsR-sp compared to the wild-type strain were consistent with the enhanced production.

Original languageEnglish
Pages (from-to)32-39
Number of pages8
JournalMicrobiological Research
Volume167
Issue number1
DOIs
Publication statusPublished - 2011 Dec 20

Keywords

  • ACCase
  • Actinomadura hibisca P157-2
  • AfsR-sp
  • Antifungal
  • MetK1-sp
  • Pradimicin

ASJC Scopus subject areas

  • Microbiology

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