Generation of multiple bioactive macrolides by hybrid modular polyketide synthases in Streptomyces venezuelae

Yeo Joon Yoon, Brian J. Beck, Beom Seok Kim, Han Young Kang, Kevin A. Reynolds, David H. Sherman

Research output: Contribution to journalArticlepeer-review

112 Citations (Scopus)


The plasmid-based replacement of the multifunctional protein subunits of the pikromycin PKS in S. venezuelae by the corresponding subunits from heterologous modular PKSs resulted in recombinant strains that produce both 12- and 14-membered ring macrolactones with predicted structural alterations. In all cases, novel macrolactones were produced and further modified by the DesVII glycosyltransferase and PikC hydroxylase, leading to biologically active macrolide structures. These results demonstrate that hybrid PKSs in S. venezuelae can produce a multiplicity of new macrolactones that are modified further by the highly flexible DesVII glycosyltransferase and PikC hydroxylase tailoring enzymes. This work demonstrates the unique capacity of the S. venezuelae pikromycin pathway to expand the toolbox of combinatorial biosynthesis and to accelerate the creation of novel biologically active natural products.

Original languageEnglish
Pages (from-to)203-214
Number of pages12
JournalChemistry and Biology
Issue number2
Publication statusPublished - 2002
Externally publishedYes

Bibliographical note

Funding Information:
National Institutes of Health grant GM48562 to D.H.S supported this research. B.J.B. was supported by a National Cancer Institute Cancer Biology Training Grant (CA09138). H.-Y.K. is grateful to the Korea Research Foundation, Support for Faculty Research Abroad Program. B.S.K. is a recipient of a Korea Science and Engineering Foundation postdoctoral fellowship. We thank Y. Lindsey and G. Florova for help in the preparation of pBK3.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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