Combined Biocatalytic and Chemical Transformations of Oleic Acid to ω‐Hydroxynonanoic Acid and α,ω‐Nonanedioic Acid

Abstract

AbstractA practical chemoenzymatic method for the synthesis of 9‐hydroxynonanoic acid and 1,9‐nonanedioic acid (i.e., azelaic acid) from oleic acid [(9Z)‐octadec‐9‐enoic acid] was investigated. Biotransformation of oleic acid into 9‐(nonanoyloxy)nonanoic acid via 10‐hydroxyoctadecanoic acid and 10‐keto‐octadecanoic acid was driven by a C‐9 double bond hydratase from Stenotrophomonas maltophilia, an alcohol dehydrogenase from Micrococcus luteus, and a Baeyer–Villiger monooxygenase (BVMO) from Pseudomonas putida KT2440, which was expressed in recombinant Escherichia coli. After production of the ester (i.e., the BVMO reaction product), the compound was chemically hydrolyzed to n‐nonanoic acid and 9‐hydroxynonanoic acid because n‐nonanoic acid is toxic to E. coli. The ester was also converted into 9‐hydroxynonanoic acid and the n‐nonanoic acid methyl ester, which can be oxygenated into the 9‐hydroxynonanoic acid methyl ester by the AlkBGT from P. putida GPo1. Finally, 9‐hydroxynonanoic acid was chemically oxidized to azelaic acid with a high yield under fairly mild reaction conditions. For example, whole‐cell biotransformation at a high cell density (i.e., 10 g dry cells/L) allowed the final ester product concentration and volumetric productivity to reach 25 mM and 2.8 mM h−1, respectively. The overall molar yield of azelaic acid from oleic acid was 58%, based on the biotransformation and chemical transformation conversion yields of 84% and 68%, respectively.magnified image