Chemistry Seminar - Theerawat Prasertanan
Theerawat Prasertanan, PhD candidate, will present a seminar.
Title:
Discovering Enzymes for Synthesis of Antibiotics Related to Kanosamine
Kanosamine is an antibiotic and antifungal, and a component of several different aminoglycosides. Kanosamine is produced by Bacillus cereus, which contains a kab operon required for kanosamine biosynthesis. Here we describe the first characterization of the encoded kab enzymes that catalyze the biosynthesis of kanosamine in three steps from glucose-6- phosphate (G6P): KabC, a NAD+-dependent dehydrogenase: KabA, a pyridoxal-5’-phosphate (PLP)-dependent aminotransferase and KabB, a kanosamine-6-phosphate (K6P) phosphatase.
We also report the steady-state kinetic parameters of three Kab enzymes along with four crystal structures of KabA: the wild-type enzyme PLP, to PMP, to a covalent adduct of PLP and K6P, and to a ternary complex of PLP and the glutamate analog glutarate. Together, our structures provide consecutive snapshots of the reaction to support the catalytic mechanism for KabA, and reveal the key active-site residues necessary for catalysis. The biosynthesis pathway of more complex structure of kanosamine, neotrehalosadiamine (NTD), will also be discussed.