Molecular insights on the biosynthesis of antitumour compounds by actinomycetes.
Bottom Line: 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.
Affiliation: Departamento de Biología Funcional and Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, 33006 Oviedo, Spain.Show MeSH
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Mentions: The utilization of combinatorial biosynthesis has become an important alternative approach for developing novel derivatives and for improving production yields of known antitumour compounds (Olano et al., 2008a; 2010). The strategies used in combinatorial biosynthesis (Fig. 3) involve gene inactivation to generate mutant strains that might accumulate novel products, expression of genes or combination of genes in different heterologous hosts including mutant strains or producers of related compounds, and mutasynthesis (Méndez and Salas, 2003; Floss, 2006; Menzella and Reeves, 2007; Kennedy, 2008; Salas and Méndez, 2009). Obviously, the application of this technology requires the isolation and characterization of the gene cluster involved in the biosynthesis of a particular antitumour compound to unravel its biosynthetic pathway.
Affiliation: Departamento de Biología Funcional and Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, 33006 Oviedo, Spain.