Zhang Yan, Eser Bekir Engin, Guo Zheng
Department of Biological and Chemical Engineering, Aarhus University, Gustav Wieds Vej 10, 8000, Aarhus, Denmark.
Chembiochem. 2021 Jun 15;22(12):2146-2153. doi: 10.1002/cbic.202100070. Epub 2021 May 2.
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.
最近发现的内源性哺乳动物脂质——羟基脂肪酸脂肪酸酯（FAHFAs），已被证明具有抗炎和抗糖尿病作用。由于它们在体内的丰度极低，因此构建一种可行的FAHFA合成方案对于其用于揭示生物学机制或进行临床试验至关重要。在此，我们展示了一种全酶法，即一种新型的体外双酶级联系统，可实现将自然界中丰富的脂肪酸有效转化为FAHFAs。使用来自嗜酸乳杆菌的两种水合酶将不饱和脂肪酸转化为各种对映体羟基脂肪酸，然后由南极假丝酵母脂肪酶A（CALA）催化与另一种脂肪酸进行酯化反应。使用这种双酶法以一锅两步操作模式在半制备规模上合成了各种FAHFAs。总之，我们证明水合酶 - CALA系统为合成光学纯的结构多样的FAHFAs提供了一条有前景的途径。
