The Biochemistry and Structural Biology of Cyanobactin Pathways: Enabling Combinatorial Biosynthesis

Abstract

Cyanobactin biosynthetic enzymes have exceptional versatility in the synthesis of natural and unnatural products. Cyanobactins are ribosomally synthesized and posttranslationally modified peptides synthesized by multistep pathways involving a broad suite of enzymes, including heterocyclases/cyclodehydratases, macrocyclases, proteases, prenyltransferases, methyltransferases, and others. Here, we describe the enzymology and structural biology of cyanobactin biosynthetic enzymes, aiming at the twin goals of understanding biochemical mechanisms and biosynthetic plasticity. We highlight how this common suite of enzymes may be utilized to generate a large array or structurally and chemically diverse compounds.

Keywords: Combinatorial biosynthesis; Cyanobactins; Cyclic peptide; Natural products; RiPP biosynthesis; Synthetic biology.