Coenzyme A thioester-mediated carbon chain elongation as a paintbrush to draw colorful chemical compounds

Abstract

The biosynthesis of various useful chemicals from simple substrates using industrial microorganisms is becoming increasingly crucial to address the challenge of dwindling non-renewable resources. As the most common intermediate substrates in organisms, Coenzyme A (CoA) thioesters play a central role in the carbon chain elongation process of their products. As a result, numerous of chemicals can be synthesized by the iterative addition of various CoA thioester extender units at a given CoA thioester primer backbone. However, these elongation reactions and the product yields are still restricted due to the low enzymatic performance and supply of CoA thioesters. This review highlights the current protein and metabolic engineering strategies used to enhance the diversity and product yield by coupling different primers, extender units, enzymes, and termination pathways, in an attempt to provide a road map for producing a more diverse range of industrial chemicals.

Keywords: Acetyl-CoA; Claisen-condensation; Malonyl-CoA; Metabolic engineering; Polyketide synthase; Thiolase.