Stereospecificity of Ketoreductase Domains 1 and 2 of the Tylactone Modular Polyketide Synthase

摘要

Tylactone synthase (TYLS) from Streptomyces fradiae is a modular polyketide synthase (PKS) that catalyzes the formation of tylactone (1), the parent 16-membered ring macrolactone aglycone precursor of the important veterinary antibiotic tylosin used in the treatment of pulmonary infections in large animals. TYLS consists of seven homodimeric modules, organized into five large proteins of subunit M_D ranging from 170 to 460 kDa, each responsible for a single round of polyketide chain extension and functional group modification (Figure 1). Although the general organization of the tylactone synthase has many features in common with the well-studied modular PKS of erythromycin biosynthesis, 6-deoxyerythronolide B (2, 6-dEB) synthase (DEBS), there are several interesting differences.