Commodity Chemicals From Engineered Modular Type I Polyketide Synthases

Methods Enzymol. 2018:608:393-415. doi: 10.1016/bs.mie.2018.04.027. Epub 2018 May 26.

Abstract

Reduced polyketides are a subclass of natural products that have a variety of medical, veterinary, and agricultural applications and are well known for their structural diversity. Although these compounds do not resemble each other, they are all made by a class of enzymes known as modular polyketide synthases (PKSs). The commonality of PKS domains/modules that compose PKSs and the understanding of the relationship between the sequence of the PKS and the structure of the compound it produces render modular PKSs as excellent targets for engineering to produce novel compounds with predicted structures. Here, we describe experimental protocols and considerations for modular PKS engineering and two case studies to produce commodity chemicals by engineered PKSs.

Keywords: Commodity chemicals; Metabolic engineering; Polyketide synthases; Protein engineering; Synthetic biology.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actinobacteria / enzymology*
  • Actinobacteria / genetics
  • Actinobacteria / metabolism
  • Adipates / metabolism
  • Amino Acid Sequence
  • Catalytic Domain
  • Computer-Aided Design
  • Ketones / metabolism
  • Metabolic Engineering / methods
  • Mutagenesis
  • Polyketide Synthases / chemistry
  • Polyketide Synthases / genetics*
  • Polyketide Synthases / metabolism
  • Polyketides / chemistry
  • Polyketides / metabolism
  • Protein Domains
  • Protein Engineering / methods*
  • Sequence Alignment
  • Streptomyces / enzymology
  • Streptomyces / genetics
  • Streptomyces / metabolism
  • Substrate Specificity

Substances

  • Adipates
  • Ketones
  • Polyketides
  • adipic acid
  • Polyketide Synthases