Structural characterization of three noncanonical NTF2-like superfamily proteins: implications for polyketide biosynthesis

Abstract

Proteins belonging to the NTF2-like superfamily are present in the biosynthetic pathways of numerous polyketide natural products, such as anthracyclins and benzoisochromanequinones. Some have been found to bebona fidepolyketide cyclases, but many of them have roles that are currently unknown. Here, the X-ray crystal structures of three NTF2-like proteins of unknown function are reported: those of ActVI-ORFA fromStreptomyces coelicolorA3(2) and its homologs Caci_6494, a protein from an uncharacterized biosynthetic cluster inCatenulispora acidiphila, and Aln2 fromStreptomycessp. CM020, a protein in the biosynthetic pathway of alnumycin. The presence of a solvent-accessible cavity and the conservation of the His/Asp dyad that is characteristic of many polyketide cyclases suggest a potential enzymatic role for these enzymes in polyketide biosynthesis.