Bleomycin biosynthesis in Streptomyces verticillus ATCC15003: A model of hybrid peptide and polyketide biosynthesis

Ben Shen, Liangcheng Du, Cesar Sanchez, Meim Chen, Daniel J. Edwards

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

The biosynthesis of bleomycins (BLMs) in Streptomyces verticillus (Sv) ATCC15003 was reviewed. Early biosynthetic studies by incorporation of isotope-labeled precursors and by isolation of biosynthetic intermediates and shunt metabolites were presented to support the hypothesis that (a) BLM is a hybrid peptide and polyketide metabolite and (b) the blm synthetase, which catalyzes the assembly of BLM from nine amino acids and an acetate, should bear the characteristics of both nonribosomal peptide synthetase (PTS) and polyketide synthase (PKS). After brief discussion of the cloning and characterization of the blm resistance genes from Sv ATCCI5003 as well as from other microorganisms, emphasis was placed on our current efforts to clone the blm biosynthesis gene cluster from Sv ATCC15003. Four cloning strategies were discussed that included chromosomal walking from the blmAB resistance genes, cloning putative PKS genes by polymerase chain reaction (PCR), cloning putative PTS genes by PCR, and the combination of chromosomal walking from the blm resistance locus and heterologous probing with PTS probes. While at least three additional peptide and one polyketide biosynthesis gene clusters were identified from Sv ATCCI5003, a putative 110- kb blm gene cluster has been cloned. Sequence analysis of 75 kb DNA provided strong support that the cloned gene cluster is responsible for BLM production.

Original languageEnglish (US)
Pages (from-to)155-171
Number of pages17
JournalBioorganic Chemistry
Volume27
Issue number2
DOIs
StatePublished - Apr 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

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