Occurrence of Two 5-Aminolevulinate Biosynthetic Pathways in Streptomyces nodosus subsp. asukaensis Is Linked with the Production of Asukamycin

We report the results of cloning genes for two key biosynthetic enzymes of different 5-aminolevulinicacid ( ALA) biosynthetic routes from Streptomyces. The genes encode the glutamyl-tRNAGlu reductase (GluTR) of the C5 pathway and the ALAsynthase ( ALAS) of the Shemin pathway. While Streptomyces coelicolorA3(2) synthesizes ALAvia the C5 route, both pathways are operational in Streptomyces nodosussubsp. asukaensis, a producer of asukamycin. In this strain, the C5 route produces ALAfor tetrapyrrolebiosynthesis; the ALAformed by the Shemin pathway serves as a precursor of the 2-amino-3-hydroxycyclopent-2- enonemoiety (C5N unit), an antibiotic component. The growth of S. nodosus and S. coelicolor strains deficient in the GluTR genes (gtr) is strictly dependent on ALAor heme supplementation, whereas the defect in the ALAS-encoding gene (hemA-asuA) abolishes the asukamycin production in S. nodosus. The recombinant hemA-asuA gene was expressed in Escherichia coli and in Streptomyces, and the encoded enzyme activity was demonstrated both in vivo and in vitro. The hemA-asuA gene is situated within a putative cluster of asukamycin biosynthetic genes. This is the first report about the cloning of genes for two different ALAbiosynthetic routes from a single bacterium.