通过微生物 12S-脂氧合酶的双氧合从多不饱和脂肪酸生物催化合成二羟基脂肪酸作为脂质介质,Biotechnology and Bioengineering

当前位置： X-MOL 学术 › Biotechnol. Bioeng. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

通过微生物 12S-脂氧合酶的双氧合从多不饱和脂肪酸生物催化合成二羟基脂肪酸作为脂质介质
Biotechnology and Bioengineering ( IF 3.5 ) Pub Date : 2021-05-14 , DOI: 10.1002/bit.27820
Tae-Hun Kim ₁ , Jin Lee ₁ , Su-Eun Kim ₁ , Deok-Kun Oh ₁

Affiliation

白三烯 (LTs) 和 maresins (MaRs) 是分别参与免疫反应和抗炎的人类脂质介质 (LMs)。这些化合物及其异构体由人类巨噬细胞和嗜中性粒细胞中的脂氧合酶 (LOX) 产生微量。这些 LM 是使用昂贵的非环境无害合成协议合成的。8种S-和 15种S -LOX 具有双重双氧合活性，此前已报道过，而 12 种S - LOX 具有双氧合活性迄今尚未报道。在这里，我们从Endozoicomonas numazuensis细菌中发现了一种具有双氧合活性的野生型 12 S -LOX，它通过双氧合从多不饱和脂肪酸中产生二羟基脂肪酸（DiHFA）作为LM。产生DiHFA的酶活性比具有双氧合活性的哺乳动物LOX的酶活性高约550倍。微生物 12 S -LOX 将 3.00 mM 花生四烯酸、二十碳五烯酸、二十二碳五烯酸和二十二碳六烯酸转化为 2.37 mM (797 mg/L) LTB4 的6-反式-8-顺式-12 S-差向异构体，1.59 mM (532 mg/L) LTB5 的6-反式-8-顺式-12 S-差向异构体，1.35 mM (498 mg/L) MaR1 _{n-3 DPA的 10-}顺式-12-反式-7 S-差向异构体, 和 1.54 mM (555 mg/L) 10-顺式-12-反式-7 S-差向异构体的 MaR1 在 2 小时内，分别比之前生物合成的高 5.3、7.6、3.1 和 5.5 倍分别报道了具有双氧合活性的微生物工程 12 S -LOX。这些发现有助于高效和环保的 LMs 生物合成，并刺激对 LMs 的生理学研究。

"点击查看英文标题和摘要"

Biocatalytic synthesis of dihydroxy fatty acids as lipid mediators from polyunsaturated fatty acids by double dioxygenation of the microbial 12S-lipoxygenase

Leukotrienes (LTs) and maresins (MaRs) are human lipid mediators (LMs) involved in immune response and anti-inflammation, respectively. These compounds and their isomers are generated in trace amounts by lipoxygenases (LOXs) in human macrophages and neutrophils. These LMs have been synthesized using nonenvironmentally benign synthetic protocols, which are expensive. 8S- and 15S-LOXs with double dioxygenating activities have previously been reported, whereas 12S-LOX with double dioxygenating activity have not been reported to date. Here, we discovered a wild-type 12S-LOX with double dioxygenating activity from the bacterium Endozoicomonas numazuensis, which produced dihydroxy fatty acids (DiHFAs) as LMs from polyunsaturated fatty acids via double dioxygenation. The enzyme activity for producing DiHFA was approximately 550-fold higher than that of mammalian LOX with double dioxygenating activity. The microbial 12S-LOX converted 3.00 mM of arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid to 2.37 mM (797 mg/L) 6-trans-8-cis-12S-epimer of LTB4, 1.59 mM (532 mg/L) 6-trans-8-cis-12S-epimer of LTB5, 1.35 mM (498 mg/L) 10-cis-12-trans-7S-epimer of MaR1_{n-3 DPA}, and 1.54 mM (555 mg/L) 10-cis-12-trans-7S-epimer of MaR1 within 2 h, which were 5.3-, 7.6-, 3.1-, and 5.5-fold higher than those biosynthesized by the previously reported microbial engineered 12S-LOX with double dioxygenating activity, respectively. These findings contribute to the efficient and environmentally friendly biosynthesis of LMs and stimulate physiological study on LMs.

更新日期：2021-07-16

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南