Structural and Preliminary Biochemical Characterization of MppQ, a PLP-Dependent Aminotransferase from Streptomyces hygroscopicus

Abstract

MppQ is an enzyme of unknown function from Streptomyces hygroscopicus that is involved in the biosynthesis of the nonproteinogenic amino acid L-enduracididine (L-End). Since L-End is a component of several peptides showing high activity against methicillin-resistant Staphylococcus aureus (MRSA), a complete understanding of its biosynthetic pathway is of utmost importance for developing chemoenzymatic routes for syntheses of novel antibiotics. In this work, we report high-resolution X-ray crystal structures of MppQ complexed with pyridoxal-5’-phosphate (PLP) and pyridoxamine-5’-phosphate (PMP). The structure of MppQ shares a fold with known Type I PLP-dependent aminotransferases, consisting of an N-terminal extension, large domain, and a small domain.