Unlocking chain length elongation to expand the long-chain dicarboxylic acid repertoire in Starmerella bombicola.

There is a rapidly growing global market of long-chain dicarboxylic acids (LCDAs) used in polymer manufacturing and other material-related industrial applications. Various types of LCDAs are considered highly value-added building blocks due to their ability to diversify the properties of the end products. Nevertheless, industrial access to very long-chain dicarboxylic acids (VLCDAs, ≥C20) is largely limited, posing a challenge to the sustainable production of green polymers. Therefore, the purpose of this study is to expand the bio-based LCDA repertoire in a non-pathogenic, oleaginous and industrially well-established yeast, Starmerella bombicola to overcome these limitations. To produce VLCDAs, an endogenous Cyp52 enzyme with a strong activity for hydroxylation of very long-chain fatty acids (VLCFAs) was selected and the intracellular fatty acid pool was modified by introducing fatty acid elongases. Furthermore, the fatty acid channeling into the ω-oxidation was strengthened. The combined metabolic engineering strategy significantly improved the production of VLCDAs from 0.3 g/L to 2.3 g/L using rapeseed oil as feedstock. The results establish an efficient bio-based route for VLCDA synthesis in S. bombicola, highlighting its potential to significantly contribute to the supply of diverse and renewable bio-based building blocks for industrial applications.