Gene clusters for bioactive natural products in actinomycetes and their use in combinatorial biosynthesis

Abstract

During the last 25 years the isolation and characterization of gene clusters involved in the biosynthesis of actinomycete secondary metabolites has permitted the elucidation of the biochemical steps involved in the production of different structural classes of bioactive compounds. The characterization of these clusters has represented a great source of genes for the generation of novel ‘unnatural natural’ compounds by using combinatorial biosynthesis. The development of more effective methods for DNA sequencing, the improvement of targeted inactivation and heterologous host expression systems has strengthened the effectiveness of combinatorial biosynthesis. For these reasons combinatorial DNA technology has become during the last decade one of the most important approaches for generating chemical structural diversity and for increasing the number of potential useful compounds