Steps towards the synthetic biology of polyketide biosynthesis
Article first published online: 7 JAN 2014
© 2013 The Authors FEMS Microbiology Letters published by John Wiley & Sons Ltd on behalf of Federation of European Microbiological Societies.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
FEMS Microbiology Letters
Special Issue: Systems and Synthetic Biology
Volume 351, Issue 2, pages 116–125, February 2014
How to Cite
Cummings, M., Breitling, R. and Takano, E. (2014), Steps towards the synthetic biology of polyketide biosynthesis. FEMS Microbiology Letters, 351: 116–125. doi: 10.1111/1574-6968.12365
- Issue published online: 24 FEB 2014
- Article first published online: 7 JAN 2014
- Accepted manuscript online: 24 DEC 2013 08:59AM EST
- Manuscript Accepted: 17 DEC 2013
- Manuscript Revised: 16 DEC 2013
- Manuscript Received: 26 NOV 2013
- BBSRC. Grant Number: BB/J014478/1
- plug-and-play biology;
- combinatorial biosynthesis;
- secondary metabolites;
- drug discovery
Nature is providing a bountiful pool of valuable secondary metabolites, many of which possess therapeutic properties. However, the discovery of new bioactive secondary metabolites is slowing down, at a time when the rise of multidrug-resistant pathogens and the realization of acute and long-term side effects of widely used drugs lead to an urgent need for new therapeutic agents. Approaches such as synthetic biology are promising to deliver a much-needed boost to secondary metabolite drug development through plug-and-play optimized hosts and refactoring novel or cryptic bacterial gene clusters. Here, we discuss this prospect focusing on one comprehensively studied class of clinically relevant bioactive molecules, the polyketides. Extensive efforts towards optimization and derivatization of compounds via combinatorial biosynthesis and classical engineering have elucidated the modularity, flexibility and promiscuity of polyketide biosynthetic enzymes. Hence, a synthetic biology approach can build upon a solid basis of guidelines and principles, while providing a new perspective towards the discovery and generation of novel and new-to-nature compounds. We discuss the lessons learned from the classical engineering of polyketide synthases and indicate their importance when attempting to engineer biosynthetic pathways using synthetic biology approaches for the introduction of novelty and overexpression of products in a controllable manner.