Purification and crystallization of modular polyketide synthase involved in Lasalocid A biosynthesis

Abstract

Lasalocid A is a broad spectrum veterinary antibiotic given to cattle. However, it exhibits cross species toxicity and thus there is a need to develop lasalocid A analogs without cross species toxic effects. Lasalocid A is a polyether ionophore and its biosynthetic pathway consists of seven polyketide synthase enzymes (Lsd11-Lsd17), one epoxidase (Lsd18), and one epoxide hydrolase (Lsd19). In this work, polyketide synthase proteins Lsd13, Lsd14, Lsd15 and Lsd16 have been purified and preliminary X-ray diffraction study of Lsd14 crystals has been carried out. Determination of high resolution atomic structure of Lsd14 using X-ray crystallography will provide new structural information that can be used for biosynthetic production of Lasalocid A analogs.