A unique fatty acid hydratase (FAH) homolog from <i>Lactobacillus acidophilus</i>, namely FA-HY1, has been recently shown to have broad substrate scope and increased regiodiversity, hydrating various double bonds of C16 to C22 fatty acids, leading to a diverse set of hydroxy fatty acids (HFAs). <i>L. acidophilus</i> possesses one other FAH homolog, FA-HY2, with 76% similarity to FA-HY1. FA-HY2 produces only 10-hydroxy HFAs from C16-C18 fatty acids. We performed comparative sequence and structure analysis of the two enzymes to shed light on promiscuity and regioselectivity differences. Four amino acid residues within the substrate binding site attracted our attention. When these residues in FA-HY2 were mutated to corresponding ones in FA-HY1, resulting variants exhibited remarkable shift in regioselectivity and substrate promiscuity in a way that is similar to FA-HY1. Our further rational and semi-rational engineering studies on the two enzymes led to FAH variants with altered regioselectivities and novel HFA products.

Engineering of fatty acid hydratases for modulation of regioselectivity and for enzymatic synthesis of novel hydroxy fatty acids and its derivatives

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.