A Bi-Enzymatic Cascade Pathway Towards FAHFAs

Recently discovered endogenous mammalian lipids fatty acid esters of hydroxy fatty acids (FAHFAs), proved to <a></a><a>have anti-inflammatory and anti-diabetic effects</a>. Due to their extremely low abundancies <i>in vivo<...

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Bibliographic Details
Main Authors: Zhang, Yan, Eser, Bekir Engin, Guo, Zheng
Format: Other/Unknown Material
Language:unknown
Published: American Chemical Society (ACS) 2021
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Online Access:http://dx.doi.org/10.26434/chemrxiv.13650629
https://ndownloader.figshare.com/files/26204369
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Summary:Recently discovered endogenous mammalian lipids fatty acid esters of hydroxy fatty acids (FAHFAs), proved to <a></a><a>have anti-inflammatory and anti-diabetic effects</a>. Due to their extremely low abundancies <i>in vivo</i>, forging a feasible scenario for FAHFA synthesis is critical for their use in uncovering biological mechanism or clinical trials. Here, we showcase a fully enzymatic approach, a novel <i>in vitro</i> bi-enzymatic cascade system, enabling an effective conversion of nature-abundant fatty acid into FAHFAs. Two hydratases <a></a><a>from <i>L. acidophilus</i> </a>were used for converting unsaturated fatty acids to various stereospecific hydroxy fatty acids, followed by esterification with another fatty acid catalyzed by <i>C. antarctica</i> lipase A (CALA). Various FAHFAs were synthesized in a preparative scale using this bi-enzymatic approach in a one-pot two-step operation mode. In all, we demonstrated that hydratase-CALA system promises a sustainable solution to the synthesis of structure-diverse stereospecific FAHFAs.