Formaldehyde: An Essential Intermediate for C1 Metabolism and Bioconversion

Formaldehyde is an intermediate metabolite of methylotrophic microorganisms that can be obtained from formate and methanol through oxidation–reduction reactions. Formaldehyde is also a one-carbon (C1) compound with high uniquely reactive activity and versatility, which is more amenable to further biocatalysis. Biosynthesis of high-value-added chemicals using formaldehyde as an intermediate is theoretically feasible and promising. This review focuses on the design of the biosynthesis of high-value-added chemicals using formaldehyde as an essential intermediate. The upstream biosynthesis and downstream bioconversion pathways of formaldehyde as an intermediate metabolite are described in detail, aiming to highlight the important role of formaldehyde in the transition from inorganic to organic carbon and carbon chain elongation. In addition, challenges and future directions of formaldehyde as an intermediate for the chemicals are discussed, with the expectation of providing ideas for the utilization of C1.