The biosynthetic gene cluster for the anticancer drug bleomycin from Streptomyces verticillus ATCC15003 as a model for hybrid peptide-polyketide natural product biosynthesis

B. Shen, L. Du, C. Sanchez, D. J. Edwards, M. Chen, J. M. Murrell

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

The hybrid peptide-polyketide backbone of bleomycin (BLM) is assembled by the BLM megasynthetase that consists of both nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) modules. BlmIX/BlmVIII/BlmVII constitute a natural hybrid NRPS/PKS/NRPS system, serving as a model for both hybrid NRPS/PKS and PKS/NRPS systems. Sequence analysis and functional comparison of domains and modules of BlmIX/BlmVIII/BlmVII with those of nonhybrid NRPS and PKS systems suggest that (1) the same catalytic sites appear to be conserved in both hybrid NRPS-PKS and nonhybrid NRPS or PKS systems, with the exception of the KS domains in the hybrid NRPS/PKS systems that are unique; (2) specific interpolypeptide linkers may play a critical role in intermodular communication to facilitate transfer of the growing intermediates between the interacting NRPS and/or PKS modules; and (3) posttranslational modification of the BLM megasynthetase has been accomplished by a single PPTase with a broad substrata specificity toward the apo forms of both acyl carrier proteins (ACPs) and peptidyl carrier proteins (PCPs).

Original languageEnglish (US)
Pages (from-to)378-385
Number of pages8
JournalJournal of Industrial Microbiology and Biotechnology
Volume27
Issue number6
DOIs
StatePublished - 2001

Keywords

  • Biosynthesis
  • Bleomycin
  • Hybrid peptide-polyketide
  • Nonribosomal peptide synthetase
  • Polyketide synthase
  • Streptomyces verticillus

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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