Molecular insights on the biosynthesis of antitumour compounds by actinomycetes
Article first published online: 18 NOV 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 144–164, March 2011
How to Cite
Olano, C., Méndez, C. and Salas, J. A. (2011), Molecular insights on the biosynthesis of antitumour compounds by actinomycetes. Microbial Biotechnology, 4: 144–164. doi: 10.1111/j.1751-7915.2010.00231.x
- Issue published online: 22 FEB 2011
- Article first published online: 18 NOV 2010
- Received 21 June, 2010; accepted 4 October, 2010.
Natural products are traditionally the main source of drug leads. In particular, many antitumour compounds are either natural products or derived from them. However, the search for novel antitumour drugs active against untreatable tumours, with fewer side-effects or with enhanced therapeutic efficiency, is a priority goal in cancer chemotherapy. Microorganisms, particularly actinomycetes, are prolific producers of bioactive compounds, including antitumour drugs, produced as secondary metabolites. Structural genes involved in the biosynthesis of such compounds are normally clustered together with resistance and regulatory genes, which facilitates the isolation of the gene cluster. The characterization of these clusters has represented, during the last 25 years, a great source of genes for the generation of novel derivatives by using combinatorial biosynthesis approaches: gene inactivation, gene expression, heterologous expression of the clusters or mutasynthesis. In addition, these techniques have been also applied to improve the production yields of natural and novel antitumour compounds. In this review we focus on some representative antitumour compounds produced by actinomycetes covering the genetic approaches used to isolate and validate their biosynthesis gene clusters, which finally led to generating novel derivatives and to improving the production yields.