Improvement of pristinamycin-producing Streptomyces pristinaespiralis by rational screening

Abstract

According to the biosynthetic pathway of pristinamycin, a rational selection procedure with u.v. mutation was performed to obtain a high pristinamycin-producing strain. Aminoacetic acid-resistant mutants (AAr), valine hydroxamate-resistant mutants (VHr), kitasamycin-resistant mutants (KTMr) and 2-deoxy-D-glucose-resistant mutants (DOGr) were selected, successively. A strain Streptomyces pristinaespiralis 12–55 with AAr, Valr, KTMr, and DOGr was obtained, and its production of pristinamycin reached 3000 u/ml which is 100 times higher than that of the parent strain S. pristinaespiralis ATCC 25486. It is inferred that S. pristinaespiralis 12–55 can alleviate catabolite repression caused by carbon sources, provide more acetic acid and valine for pristinamycin biosynthesis and increase its resistance to pristinamycin produced by itself, all of which are favorable for pristinamycin production. The subculture experiments indicated that the hereditary character of high productivity of S. pristinaespiralis 12–55 is stable. The pristinamycin production of S. pristinaespiralis 12–55 in a 15-l fermentor could reach 3010 u/ml after a 56 h batch fermentation.