Discovery, biosynthesis, and rational engineering of novel enterocin and wailupemycin polyketide analogues

John A. Kalaitzis*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

6 Citations (Scopus)

Abstract

The marine actinomycete Streptomyces maritimus produces a structurally diverse set of unusual polyketide natural products including the major metabolite enterocin. Investigations of enterocin biosynthesis revealed that the unique carbon skeleton is derived from an aromatic polyketide pathway which is genetically coded by the 21.3 kb enc gene cluster in S. maritimus. Characterization of the enc biosynthesis gene cluster and subsequent manipulation of it via heterologous expression and/or mutagenesis enabled the discovery of other enc-based metabolites that were produced in only very minor amounts in the wild type. Also described are techniques used to harness the enterocin biosynthetic machinery in order to generate unnatural enc-derived polyketide analogues. This review focuses upon the molecular methods used in combination with classical natural products detection and isolation techniques to access minor metabolites of the S. maritimus secondary metabolome.

Original languageEnglish
Title of host publicationMetabolomics tools for natural product discovery
Subtitle of host publicationmethods and protocols
EditorsUte Roessner, Daniel Anthony Dias
Place of PublicationTotowa, NJ
PublisherHumana Press
Pages171-189
Number of pages19
ISBN (Electronic)9781627035774
ISBN (Print)9781627035767
DOIs
Publication statusPublished - 2013
Externally publishedYes

Publication series

NameMethods in Molecular Biology
Volume1055
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • Enterocin
  • Wailupemycin
  • Polyketide
  • Biosynthesis
  • Type II polyketide synthase
  • Biosynthesis gene cluster
  • Mutasynthesis
  • Heterologous expression
  • Enzymatic synthesis

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