Get access
Advertisement

Production of Macrocyclic Sesqui- and Diterpenes in Heterologous Microbial Hosts: A Systems Approach to Harness Nature’s Molecular Diversity

Authors

  • Prof. Dr. Thomas Brück,

    Corresponding author
    1. Fachgebiet für Industrielle Biokatalyse, Zentrum für Weiße Biotechnologie, Fakultät für Chemie, Technische Universität München, Lichtenberg Str. 4, 85748 Garching (Germany), Fax: (+49) 89-289-13255
    • Fachgebiet für Industrielle Biokatalyse, Zentrum für Weiße Biotechnologie, Fakultät für Chemie, Technische Universität München, Lichtenberg Str. 4, 85748 Garching (Germany), Fax: (+49) 89-289-13255===

    Search for more papers by this author
  • Prof. Dr. Robert Kourist,

    1. Juniorprofessor für Mikrobielle Biotechnologie, Dept. of Biology and Biochemistry, Ruhr Universität Bochum, Universitätstr. 150, 44780 Bochum (Germany)
    Search for more papers by this author
  • Dr. Bernhard Loll

    1. Institut für Chemie und Biochemie, Abteilung Strukturbiochemie, Freie Universität Berlin, Takusstr. 6, 14195 Berlin (Germany), Fax: (+49) 030-838-54936
    2. moloX GmbH, Takusstr. 6, 14195 Berlin, (Germany)
    Search for more papers by this author

Abstract

Macrocyclic sesqui- (C15) and diterpenes (C20) are a functionally diverse group of natural products with versatile bioactivities encompassing anticancer, antimicrobial and insecticidal agents. Structural complexity prevents economically efficient total synthesis of these higher terpenoids. Heterologous production in recombinant whole-cell biocatalysts is an emerging alternative. Conventional cell systems (i.e., Escherichia coli and Saccharomyces cerevisiae) frequently suffer from low volumetric yields. However, recent combinations of metabolic, enzyme and process engineering in conjunction with systems biology allow significant improvements towards economically viable processes. This Review analyzes research trends in the dynamic fields of terpene-centered microbial cell systems and enzyme engineering. An outlook is given on emerging microbial hosts, which may simplify cellular engineering towards higher product titers.

Get access to the full text of this article

Ancillary