Recent advances in the structural biology of modular polyketide synthases and nonribosomal peptide synthetases

Abstract

Polyketides and nonribosomal peptides are an important class of natural products with useful bioactivities. These compounds are similarly biosynthesized using enzymes with modular structures despite having different physicochemical properties. These enzymes are attractive targets for bioengineering to produce "unnatural" natural products owing to their modular structures. Therefore, their structures have been studied for a long time; however, the main focus was on truncated-single domains. Surprisingly, there is an increasing number of the structures of whole modules reported, most of which have been enabled through the recent advances in cryogenic electron microscopy technology. In this review, we have summarized the recent advances in the structural elucidation of whole modules.

Keywords: Cryogenic electron microscopy; Modular enzyme; Nonribosomal peptide; Polyketide; Structural biology; X-ray crystallography.