Engineering for the Production of Renewable Dicarboxylic Acids from Fatty Acid Based Feedstocks

Verdezyne is an industrial biotechnology company that uses engineered yeast to convert fatty acids derived from non-food sources to several different dicarboxylic acids, or diacids. These diacids are commonly used in a diverse range of industrial and consumer products. An example is the twelve-carbon-long dodecanedioic acid, which is found in products from toothbrushes and cosmetics to lubricants, adhesives and car parts. Another example is adipic acid, which is mostly used as a monomer for the production of nylon.  Both of these diacids are produced from petroleum-based inputs. Verdezyne has developed technologies with the intent of commercializing processes that replace important petroleum-based chemical intermediates with renewable and sustainable alternatives.

The production of diacids from long chain fatty acids presents numerous challenges from metabolic engineering through fermentation to purification. Some of the challenges at the level of metabolic engineering include the characterization of enzyme substrate specificity and the appropriate regulation of enzyme expression and intracellular metabolite trafficking. In order to exercise greater control over the length of the product(s) formed by our engineered strains, we have also performed some targeted protein engineering of enzymes in the two key pathways that we have manipulated, namely omega- and beta-oxidation, which occur in the cytoplasm and the peroxisome, respectively. The omega-oxidation pathway oxidizes the terminal carbon of a fatty acid to produce a diacid, while beta-oxidation shortens the diacid to produce one acetyl-CoA and a diacid that is shorter by two carbons. This presentation will focus on some of the genetic changes and protein engineering that have allowed for the production of diacids of different chain lengths from long chain fatty acids as the starting feedstock.