Bioconversion capacity of Streptomyces sp GE44282, a producer of the antibiotics heneicomycin and aurodox.

Streptomyces sp GE44282 was isolated in the course of a screening program for novel antibiotics. It co-produces heneicomycin and aurodox, two kirromycin-type antibiotics, which differ by the presence of an hydroxyl group at the C30 position of aurodox. Heneicomycin is converted into aurodox both by growing and resting cells of Streptomyces sp GE44282 and by the producer of aurodox, Streptomyces goldiniensis ATCC 21386. This bioconversion of heneicomycin is substrate-specific and is not observed using the producer of heneicomycin, Streptomyces filippiniensis NRRL 11044. The three strains show very similar taxonomic characteristics. These results suggest that heneicomycin is a precursor of aurodox, the production of which depends on the bioconversion capability expressed by the strain.

Induction of resistance to aurodox by aurodox in the antibiotic-producing culture, Streptomyces goldiniensis.

The sensitivity of protein and aurodox synthesis to aurodox was examined in relationship to the development of resistance to aurodix on Streptomyces goldiniensis during fermentation. It was found that the culture remains sensitive to the antibiotic as long as no aurodox is present in the medium. Resistance only develops when aurodox is present, either exogenously added or endogenously synthesized by the culture. These observations suggest that the development of resistance is an inducible process, and evidence is presented indicating that aurodox induces a specific resistance system in S. goldiniensis.

Increased production of the antibiotic aurodox (X-5108) by aurodox-resistant mutants.

Conventional strain and media improvement techniques were of limited success in increasing yields of the antibiotic aurodox (X-5108) above 0.5 g/liter. Higher yields were obtained by reversion of a zero producer followed by the selection of mutants resistant to aurodox. Resistant strains of Streptomyces goldiniensis ATCC 21386 able to grow on 2 g/liter of aurodox produced greater than 2.5 g/liter of antibiotic. The rate of yield increase leveled off as the strains became resistant to greater than 2 g/liter of aurodox. These strains, in contrast to those sensitive to aurodox, gave a positive response to conventional mutagenic methods for further yield increases.

Feedback inhibition of the synthesis of an antibiotic: aurodox (X-5108).

The effect of aurodox on its own biosynthesis by Streptomyces goldiniensis was studied. It was found that addition of exogenous aurodox inhibits further accumulation of aurodox by the antibiotic-producing culture. Both long term fermentation studies with aurodox-14C and precursor incorporation studies over short time periods indicated that aurodox synthesis was regulated by feedback inhibition. The concentration of aurodox required to completely block further synthesis of the antibiotic was about 400 microng/ml. This is the same as the maximum concentration of aurodox normally accumulated by the culture used in this study. Antibiotic synthesis was inhibited not only by aurodox but also by some structural analogs of aurodox including several having no antibacterial activity. This effect was immediate and readily reversible, indicating that it could be due to inhibition of an enzyme(s) involved in the biosynthesis of aurodox.