Hybrid peptide-polyketide natural products: Biosynthesis and prospects toward engineering novel molecules

Liangcheng Du, César Sánchez, Ben Shen

Research output: Contribution to journalReview article

146 Scopus citations

Abstract

The structural and catalytic similarities between modular non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) inspired us to search for hybrid NRPS-PKS systems. By examining the biochemical and genetic data known to date for the biosynthesis of hybrid peptide-polyketide natural products, we show (1) that the same catalytic sites are conserved between the hybrid NRPS-PKS and normal NRPS or PKS systems, although the ketoacyl synthase domain in NRPS/PKS hybrids is unique, and (2) that specific interpolypeptide linkers exist at both the C- and N-termini of the NRPS and PKS proteins, which presumably play a critical role in facilitating the transfer of the growing peptide or polyketide intermediate between NRPS and PKS modules in hybrid NRPS-PKS systems. These findings provide new insights for intermodular communications in hybrid NRPS-PKS systems and should now be taken into consideration in engineering hybrid peptide-polyketide biosynthetic pathways for making novel "unnatural" natural products.

Original languageEnglish (US)
Pages (from-to)78-95
Number of pages18
JournalMetabolic Engineering
Volume3
Issue number1
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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