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

43 Citations (Scopus)

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 - Dec 1 2001

Fingerprint

Peptide Synthases
Polyketides
Polyketide Synthases
Biosynthesis
Bleomycin
Streptomyces
Multigene Family
Biological Products
Peptides
Genes
Pharmaceutical Preparations
Acyl Carrier Protein
Post Translational Protein Processing
Sequence Analysis
Catalytic Domain
Carrier Proteins

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

The biosynthetic gene cluster for the anticancer drug bleomycin from Streptomyces verticillus ATCC15003 as a model for hybrid peptide-polyketide natural product biosynthesis. / Shen, B.; Du, L.; Sanchez, C.; Edwards, D. J.; Chen, M.; Murrell, J. M.

In: Journal of Industrial Microbiology and Biotechnology, Vol. 27, No. 6, 01.12.2001, p. 378-385.

Research output: Contribution to journalArticle

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