Genetic regulation and manipulation for natural product discovery

Appl Microbiol Biotechnol. 2016 Apr;100(7):2953-65. doi: 10.1007/s00253-016-7357-3. Epub 2016 Feb 10.

Abstract

Natural products are an important source of modern medical development, e.g., antibiotics, anticancers, immune modulators, etc. and will continue to be a powerful driving force for the discovery of novel potential drugs. In the heterologous hosts, natural products are biosynthesized using dedicated metabolic networks. By gene engineering, pathway reconstructing, and enzyme engineering, metabolic networks can be modified to synthesize novel compounds containing enhanced structural feature or produce a large quantity of known valuable bioactive compounds. The review introduces some important technical platforms and relevant examples of genetic regulation and manipulation to improve natural product titers or drive novel secondary metabolite discoveries.

Keywords: Discovery; Natural product; Regulation and manipulation.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / biosynthesis
  • Anti-Bacterial Agents / isolation & purification
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / metabolism
  • Aspergillus nidulans / genetics*
  • Aspergillus nidulans / metabolism
  • Biological Products / isolation & purification
  • Biological Products / metabolism*
  • Biosynthetic Pathways
  • Drug Discovery*
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Gene Expression Regulation
  • Genetic Engineering / methods*
  • Glycopeptides / biosynthesis
  • Glycopeptides / isolation & purification
  • Humans
  • Immunologic Factors / biosynthesis
  • Immunologic Factors / isolation & purification
  • Naphthoquinones / isolation & purification
  • Naphthoquinones / metabolism
  • Secondary Metabolism
  • Streptomyces / genetics*
  • Streptomyces / metabolism

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Biological Products
  • Glycopeptides
  • Immunologic Factors
  • Naphthoquinones