Cancer research yields unexpected results

Louis Pasteur once said “Chance favors the prepared mind”. Surely any scientist can attest to this. Discoveries of things  like artificial sweeteners, Teflon, and penicillin were all unintended products of unrelated research. Recently, scientists at the Duke Cancer Institute studying the microevolution of enzymes involved in cancer happened upon a missing enzymatic link in a very unrelated area of research that has less to do with cancer than with the production of carpeting, apparel, and auto parts(1).

Nylon is a critical component in all of those products, any many, many more. Production nylon requires a compound called adipic acid. This intermediary, one of the most widely used chemicals in the world,  is produced from fossil fuels and pollution released from its refinement process is a leading contributor to global warming. To date, there hasn’t been a “green” way of producing adipic acid because there is one critical enzyme in the synthesis pathway that isn’t available: 2-hydroxyadipate dehydrogenase.

Biochemical engineering on its own had not produced a sufficient dehydrogenase to do the job. Enter the cancer researchers.   Cancer involves the microevolution of cells which offer benefits to the cells, sometimes including gain-of-function mutations in metabolic enzymes. Duke researchers identified a  mutation in glioblastomas that alters the function of isocitrate dehydrogenase. The Duke team applied their knowledge of how enzymes change during cancer to lay the blueprints on a new method for producing  clean, green, adipic acid. By using the same mutation framework, the scientist found that they could create enzymes from homoisocitrate dehydrogenase found in yeasts and bacteria that were capable of producing adipic acid from inexpensive sugars. The group still needs to scale up their production, a process that will still require a tremendous amount of work.

1.  Reitman, Z. et al. (2012) Enzyme redesign guided by cancer-derived IDH1 mutations.  Nat. Chem. Biol.  Available online.

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