Influence of ancillary genes, encoding aspects of methionine metabolism, on tylosin biosynthesis in Streptomyces fradiae

The tylosin-biosynthetic (tyl) gene cluster of Streptomyces fradiae contain s ancillary genes that encode functions normally associated with primary me tabolism. These can be disrupted without loss of viability, since equivalen t genes (presumably used for 'housekeeping' purposes) are also present else where in the genome. The tyl cluster also contains two genes that encode pr oducts unlike any proteins in the databases. Two ancillary genes, metF (enc oding N-5,N-10-methylenetetrahydrofolate reductase) and metK, encoding S-ad enosylmethionine synthase, flank one of the 'unknown' genes (orf9) in the t yl cluster. In a strain of S. ftadiae in which all three of these genes wer e disrupted, tylosin production was reduced, although this effect was obscu red in media supplemented with glycine betaine which can donate methyl grou ps to the tetrahydrofolate pool. Apparently, one consequence of the recruit ment of ancillary genes into the tyl cluster is enhanced capacity for trans methylation during secondary metabolism.