High Production of Azelaic Acid from Nonanoic Acid in an Adaptive Laboratory Evolved Escherichia coli Strain with Alkane Degradation Pathway

Abstract

Azelaic acid, which was found to have a beneficial effect on a number of hyperpigmentation disorders, has been used acne medication. In the selection of cosmetics and medicines, consumers have escalated into the degree of concern which was the psychological syndrome, chemophobia (i.e., the fear of chemicals). Biocatalytic production of therapeutic and cosmetics chemical can overcome this syndrome. Azelaic acid can be produced from nonanoic acid by oxidation of the terminal methyl group, what is called ω-oxidation. Chemical ω-oxidation of nonactivated tertiary methyl groups remains difficult due to the unreactive nature of these bonds. We can employ an alkane degradation pathway for biocatalytic production of azelaic acid in Escherichia coli. This system was observed oxidation in positions only terminal methyl carbons, indicating that this system has high specificity activity. Nonanoic acid, one of the medium-chain fatty acid, which can undergo two oxidation steps to form azelaic acid. However, since nonanoic acid is toxicity, wild type MG 1655 strain does not grow on nonanoic acid efficiently. In this study, we constructed an evolved strain that can grow well on nonanoic acid using the adaptive laboratory evolution method. We identified and characterized mutations found in the evolved strain and applied the strain for the production of azelaic acid by expressing the alkane degradation pathway.