Genetic engineering of antibiotic biosynthesis for the generation of new aminocoumarins.

The aminocoumarin antibiotics novobiocin, clorobiocin and coumermycin A(1) are inhibitors of gyrase and highly effective antibacterial agents. Their biosynthetic gene clusters have been cloned from the respective Streptomyces producer strains, and the function of nearly all genes contained therein has been elucidated by genetic and biochemical methods. Efficient methods have been developed for the genetic manipulation and the heterologous expression of the clusters, and more than 100 new derivatives of these antibiotics have been generated by metabolic engineering, mutasynthesis and chemoenzymatic synthesis, providing a model for the power of genetic and genomic methods for the generation of new bioactive compounds.