Eun-Ji Seo, Hyo-Ran Lee, Se-Yeun Hwang, Deok-Kun Oh, Yong-Uk Kwon, Katharina Köchl, Bettina Nestl, Jin-Byung Park, Uwe T. Bornscheuer
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引用次数: 0
Abstract
Lipoxygenases catalyze the dioxygenation of polyunsaturated fatty acids. Notably, most microbial lipoxygenases including the lipoxygenase from Pseudomonas aeruginosa (Pa-LOX) catalyze oxygenation of linoleic acid and arachidonic acid into 13S-hydroperoxyoctadecenoic acid (13S-HPODE) and 15S-hydroperoxyeicosatetraenoic acid (15S-HPETE), respectively. Therefore, this study has focused on modification of positional specificity or regioselectivity of Pa-LOX. The linoleic acid oxygenations and substrate-docking simulations suggested that the regioselectivity of Pa-LOX might depend on the geometry of the hydrocarbon tail-binding cavity. Therefore, the interior end of the substrate-binding cavity was enlarged to make C10 instead of C13 face the iron active site. Remarkably, the M434G mutation led to alteration of the oxygenation products from 15S-hydroxyeicosatetraenoic acid (15S-HPETE) to 11S-HPETE as the major product from arachidonic acid. On the other hand, the Y609G substitution allowed the formation of 8S-HPETE from arachidonic acid. 8S-HPETE was recovered after reduction by tris(2-carboxyethyl)phosphine hydrochloride with an isolated yield of 62% with a purity of 94% via Escherichia coli-based whole-cell biocatalysis, solvent extraction, and silica gel chromatography. This is the first report of the production of 11S-HPETE and 8S-HPETE from arachidonic acid at high conversions. Therefore, this study contributes to the preparation of biologically active oxylipins from renewable fatty acids in a sustainable way.
期刊介绍:
ACS Sustainable Chemistry & Engineering is a prestigious weekly peer-reviewed scientific journal published by the American Chemical Society. Dedicated to advancing the principles of green chemistry and green engineering, it covers a wide array of research topics including green chemistry, green engineering, biomass, alternative energy, and life cycle assessment.
The journal welcomes submissions in various formats, including Letters, Articles, Features, and Perspectives (Reviews), that address the challenges of sustainability in the chemical enterprise and contribute to the advancement of sustainable practices. Join us in shaping the future of sustainable chemistry and engineering.