RARE Approach Advances Synthetic Production of Industrial Chemicals

Achievement date: 

Massachusetts Institute of Technology (MIT) researchers have found a novel approach for producing aldehydes--a class of chemicals with many industrial uses such as flavors, fragrances, and precursors to new pharmaceuticals—by microbial synthesis. This research was supported by the NSF-funded Synthetic Biology Engineering Research Center (Synberc), headquartered at the University of California (UC) Berkeley.


Several aldehydes have the potential for high-value applications and large markets, leading to a surge in commercial focus on microbial aldehyde synthesis in recent years. However, a major challenge has been finding a process that acts quickly enough to beat aldehydes’ behavior of rapidly converting to their corresponding alcohols. This Synberc-sponsored research yielded a new approach to microbial production of aldehydes that overcomes that challenge, thus expanding the classes of chemicals that can be produced using metabolic engineering and biocatalysis.


Aldehydes--organic compounds formed by the oxidation of alcohols--are responsible for flavors and fragrances present in some plants but are not known to accumulate in most natural microorganisms. Although metabolic pathways that result in alcohol synthesis via aldehyde intermediates were long known, this research succeeded in minimizing the rapid endogenous conversion of aldehydes into their corresponding alcohols and provides a foundation for microbial aldehyde synthesis.

Using an E. coli chassis (E. coli is a model organism in biological engineering; "chassis" means the conceptual extension of a living cell), researchers found a way it could be engineered to have reduced aromatic aldehyde reduction, leading to the RARE chassis. The RARE chassis was further investigated for specific outcomes, overcoming previous limitations and enhancing bioconversion of aldehydes to other chemical classes.