Phenotypic changes associated with loss of expression of tylosin biosynthesis and resistance genes in Streptomyces fradiae

Abstract

Two mutants of the tylosin-producing Streptomyces fradiae defective in the biosynthesis of the macrolide antibiotic tylosin were isolated from colonies derived from regenerated protoplasts. Both strains were unable to carry out any of at least seven tylosin biosynthetic steps and were sensitive to tylosin. One strain, JS82, was also more sensitive to chloramphenicol (Cm), mitomycin C (Mc), hygromycin B (Hm) and kanamycin (Km) than its parent strain. The other strain, JS87, was also more sensitive to Cm than wild type but expressed normal levels of resistance to Mc and Hm. Both strains expressed genetic instabilities associated with auxotrophy or expression of antibiotic resistance. Since the genetic instabilities were not due to defective error-free or error-prone DNA repair, they appear to be due to genetic rearrangements associated with the deletion or amplification of sequences linked to and perhaps encompassing tylosin biosynthesis genes.