Cloning, sequencing, and characterization of the pradimicin biosynthetic gene cluster of Actinomadura hibisca P157-2

Byung Chul Kim, Jung Min Lee, Jong Seog Ahn, Beom Seok Kim

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Pradimicins are potent antifungal antibiotics having an unusual dihydrobenzo[α]naphthacenequinone aglycone substituted with D-alanine and sugars. Pradimicins are polyketide antibiotics produced by Actinomadura hibisca P157-2. The gene cluster involved in the biosynthesis of pradimicins was cloned and sequenced. The pradimicin gene cluster was localized to a 39-kb DNA segment and its involvement in the biosynthesis of pradimicin was proven by gene inactivation of prmA and prmB (ketosynthases α and β). The pradimicin gene cluster consists of 28 open reading frames (ORFs), encoding a type II polyketide synthase (PKS), the enzymes involved in sugar biosynthesis and tailoring enzymes as well as two resistance proteins. The deduced proteins showed strong similarities to the previously validated gene clusters of angucyclic polyketides such as rubromycin, griseorhodin, and fredericamycin. From the pradimicin gene cluster, prmP3 encoding a component of the acetyl-CoA carboxylase complex was disrupted. The production levels of pradimicins of the resulting mutants decreased to 62% of the level produced by the wild-type strain, which indicate that the acetyl-CoA carboxylase gene would have a significant role in the production of pradimicins through supplying the extender unit precursor, malonyl-CoA.

Original languageEnglish
Pages (from-to)830-839
Number of pages10
JournalJournal of Microbiology and Biotechnology
Volume17
Issue number5
Publication statusPublished - 2007 May 1

Fingerprint

Cloning
Multigene Family
Organism Cloning
Genes
Polyketides
Acetyl-CoA Carboxylase
Biosynthesis
Antibiotics
Polyketide Synthases
Malonyl Coenzyme A
Sugars
Antifungal Agents
Enzymes
Gene Silencing
Proteins
Alanine
Open Reading Frames
Anti-Bacterial Agents
DNA

Keywords

  • Actinomadura hibisca
  • Polyketide biosynthesis
  • Pradimicin
  • Type II polyketide synthase

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology
  • Microbiology
  • Bioengineering

Cite this

Cloning, sequencing, and characterization of the pradimicin biosynthetic gene cluster of Actinomadura hibisca P157-2. / Kim, Byung Chul; Lee, Jung Min; Ahn, Jong Seog; Kim, Beom Seok.

In: Journal of Microbiology and Biotechnology, Vol. 17, No. 5, 01.05.2007, p. 830-839.

Research output: Contribution to journalArticle

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