A Bi‐Enzymatic Cascade Pathway towards Optically Pure FAHFAs. (2nd May 2021)

• Record Type: Journal Article
• Authors: Zhang, Yan; Eser, Bekir Engin; Guo, Zheng
• Is Part Of: Chembiochem. Volume 22:Number 12(2021)
• Page Start: 2146
• Page End: 2153
• Publication Date: 2021-05-02
• Subjects: bioactive FAHFAs -- enzymatic synthesis -- fatty acid hydratase -- lipase -- renewable biomass; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202100070
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Recently discovered endogenous mammalian lipids, fatty acid esters of hydroxy fatty acids (FAHFAs), have been proved to have anti‐inflammatory and anti‐diabetic effects. Due to their extremely low abundancies in vivo, forging a feasible scenario for FAHFA synthesis is critical for their use in uncovering biological mechanisms or in clinical trials. Here, we showcase a fully enzymatic approach, a novel in vitro bi‐enzymatic cascade system, enabling an effective conversion of nature‐abundant fatty acids into FAHFAs. Two hydratases from Lactobacillus acidophilus were used for converting unsaturated fatty acids to various enantiomeric hydroxy fatty acids, followed by esterification with another fatty acid catalyzed by Candida antarctica lipase A (CALA). Various FAHFAs were synthesized in a semi‐preparative scale using this bi‐enzymatic approach in a one‐pot two‐step operation mode. In all, we demonstrate that the hydratase‐CALA system offers a promising route for the synthesis of optically pure structure‐diverse FAHFAs. Abstract : Full enzymatic synthesis of FAHFAs : Various hydroxy fatty acids with different −OH positions can be synthesized from renewable fatty acids by wild‐type and engineered fatty acid hydratases, which can be cascaded with lipase to prepare value‐added FAHFAs with potential medical value.