Microbial Biotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup-Si, 56212, Republic of Korea.
Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Pocheon-Si, Gyeonggi-do, 11160, Republic of Korea.
Sci Rep. 2020 Nov 2;10(1):18849. doi: 10.1038/s41598-020-76005-5.
Omega-3 polyunsaturated fatty acids (PUFAs) have been known to have beneficial effects in the prevention of various diseases. Recently, it was identified that the bioactivities of omega-3 are related to lipid mediators, called pro-resolving lipid mediators (SPMs), converted from PUFAs, so they have attracted much attention as potential pharmaceutical targets. Here, we aimed to build an efficient production system composed of enzymatic and chemical catalysis that converts docosahexaenoic acid (DHA) into lipid mediators. The cyanobacterial lipoxygenase, named Osc-LOX, was identified and characterized, and the binding poses of enzyme and substrates were predicted by ligand docking simulation. DHA was converted into three lipid mediators, a 17S-hydroxy-DHA, a 7S,17S-dihydroxy-DHA (RvD5), and a 7S,15R-dihydroxy-16S,17S-epoxy-DPA (new type), by an enzymatic reaction and deoxygenation. Also, two lipid mediators, 7S,15R,16S,17S-tetrahydroxy-DPA (new type) and 7S,16R,17S-trihydroxy-DHA (RvD2), were generated from 7S,15R-dihydroxy-16S,17S-epoxy-DPA by a chemical reaction. Our study suggests that discovering new enzymes that have not been functionally characterized would be a powerful strategy for producing various lipid mediators. Also, this combination catalysis approach including biological and chemical reactions could be an effective production system for the manufacturing lipid mediators.
ω-3 多不饱和脂肪酸 (PUFA) 已被证实具有预防多种疾病的有益作用。最近，人们发现 ω-3 的生物活性与脂质介质有关，这些脂质介质称为促分解脂质介质 (SPM)，由 PUFAs 转化而来，因此它们作为潜在的药物靶点引起了广泛关注。在这里，我们旨在构建一种由酶和化学催化组成的高效生产系统，将二十二碳六烯酸 (DHA) 转化为脂质介质。鉴定并表征了一种名为 Osc-LOX 的蓝藻脂氧合酶，并通过配体对接模拟预测了酶和底物的结合构象。通过酶促反应和脱氧反应，DHA 转化为三种脂质介质，即 17S-羟基-DHA、7S,17S-二羟基-DHA（RvD5）和 7S,15R-二羟基-16S,17S-环氧-DPA（新型）。此外，通过化学反应，从 7S,15R-二羟基-16S,17S-环氧-DPA 生成两种脂质介质，即 7S,15R,16S,17S-四羟基-DPA（新型）和 7S,16R,17S-三羟基-DHA（RvD2）。我们的研究表明，发现具有未被功能表征的新酶将是生产各种脂质介质的有力策略。此外，这种包括生物和化学反应的组合催化方法可能是制造脂质介质的有效生产系统。
