Engineering Streptomyces coelicolor for heterologous expression of secondary metabolite gene clusters
Article first published online: 26 OCT 2010
© 2010 The Authors. Journal compilation © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd
Special Issue: Crystal ball and Streptomyces Special issue. Guest Editors: Hildgund Schrempf, Paul Dyson and Sergey Zotchev
Volume 4, Issue 2, pages 207–215, March 2011
How to Cite
Gomez-Escribano, J. P. and Bibb, M. J. (2011), Engineering Streptomyces coelicolor for heterologous expression of secondary metabolite gene clusters. Microbial Biotechnology, 4: 207–215. doi: 10.1111/j.1751-7915.2010.00219.x
- Issue published online: 22 FEB 2011
- Article first published online: 26 OCT 2010
- Received 10 July, 2010; accepted 3 September, 2010.
We have constructed derivatives of Streptomyces coelicolor M145 as hosts for the heterologous expression of secondary metabolite gene clusters. To remove potentially competitive sinks of carbon and nitrogen, and to provide a host devoid of antibiotic activity, we deleted four endogenous secondary metabolite gene clusters from S. coelicolor M145 – those for actinorhodin, prodiginine, CPK and CDA biosynthesis. We then introduced point mutations into rpoB and rpsL to pleiotropically increase the level of secondary metabolite production. Introduction of the native actinorhodin gene cluster and of gene clusters for the heterologous production of chloramphenicol and congocidine revealed dramatic increases in antibiotic production compared with the parental strain. In addition to lacking antibacterial activity, the engineered strains possess relatively simple extracellular metabolite profiles. When combined with liquid chromatography and mass spectrometry, we believe that these genetically engineered strains will markedly facilitate the discovery of new compounds by heterologous expression of cloned gene clusters, particularly the numerous cryptic secondary metabolic gene clusters that are prevalent within actinomycete genome sequences.