The tylosin-biosynthetic genes of Streptomyces fradiae

The tylosin-biosynthetic (tyl) gene cluster occupies about 1% of the genome of Streptomyces fradiae and includes at least 43 open reading frames. In a ddition to structural genes required for tylosin production, the tyl cluste r contains three resistance determinants and several regulatory genes. Tylo sin production is evidently controlled by pathway-specific and pleiotropic regulators with the likely involvement of gamma -butyrolactone signalling f actors. Accumulation of the polyketide aglycone is controlled by glycosylat ed macrolides and optimal performance of the complex polyketide synthase en zyme requires the activity of an editing thioesterase.