The design of an enzyme catalyzing a new type of reaction was inspired by how cancer cells mutate, reports a paper published online this week in Nature Chemical Biology. The success of this reaction has implications for both the biocatalytic production of the commodity chemical adipic acid, a precursor for nylon, and in the design of other proteins.
A challenge in synthesizing chemicals has been how to use more enzymes to catalyze chemical reactions en route to a molecule of interest, thereby avoiding the use of harsh solvents or other hurdles that can be required. Application of enzymes in industrial-scale chemical conversions is often limited, however, by not having an enzyme that is known to catalyze a reaction of interest.
Hai Yan and colleagues show that cancer mutations can be harnessed for such use. The authors noted that the missing reaction from a biocatalytic process to make the widely-used adipic acid was very similar to the reaction catalyzed by a mutant of isocitrate dehydrogenase identified in cancer cells. By making the same mutations to the related homoisocitrate dehydrogenase, the authors were able to convert 2-oxoadipate to (R)-2-hydroxyadipate, as desired.