Synthetic Biology in Metabolic Engineering: From Complex Biochemical Pathways to Compartmentalized Metabolic Processes - a Vitamin Connection

Abstract

Vitamin B12 (cobalamin) is a remarkable nutrient not only because of its structural complexity but also because it is only synthesized by certain bacteria. In order to understand its biosynthesis and to enhance its production, metabolic engineering and synthetic biology strategies have been applied to elucidate this metabolic process; the results of which have shown that intermediates in the pathway are passed from one enzyme to the next by substrate channeling. Knowledge of the pathway is also being used in the design of vitamin analogs that have potential as drug-delivery vehicles. Once its synthesis is complete, cobalamin is required as either a coenzyme or cofactor in a number of different metabolic processes. Some cobalamin-dependent enzymes are found encased within bacterial microcompartments, proteinaceous organelles that house a specific metabolic pathway. The potential to develop these supra-macromolecular structures into bespoke bioreactors by replacing the embedded pathway is discussed. Keywords: synthetic biology; vitamin B 12 ; substrate channeling; cobalamin biosynthesis methyltransferases; bacterial microcompartments