An Jung-Ung, Song Yong-Seok, Kim Kyoung-Rok, Ko Yoon-Joo, Yoon Do-Young, Oh Deok-Kun
Department of Integrative Bioscience and Biotechnology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea.
National Center for Inter-University Research Facilities (NCIRF), Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
Nat Commun. 2018 Jan 9;9(1):128. doi: 10.1038/s41467-017-02543-8.
Hepoxilins (HXs) and trioxilins (TrXs) are involved in physiological processes such as inflammation, insulin secretion and pain perception in human. They are metabolites of polyunsaturated fatty acids (PUFAs), including arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, formed by 12-lipoxygenase (LOX) and epoxide hydrolase (EH) expressed by mammalian cells. Here, we identify ten types of HXs and TrXs, produced by the prokaryote Myxococcus xanthus, of which six types are new, namely, HXB, HXD, HXE, TrXB, TrXD and TrXE. We succeed in the biotransformation of PUFAs into eight types of HXs (>35% conversion) and TrXs (>10% conversion) by expressing M. xanthus 12-LOX or 11-LOX with or without EH in Escherichia coli. We determine 11-hydroxy-eicosatetraenoic acid, HXB, HXB, HXD, TrXB and TrXD as potential peroxisome proliferator-activated receptor-γ partial agonists. These findings may facilitate physiological studies and drug development based on lipid mediators.
肝氧素（HXs）和三氧素（TrXs）参与人体的炎症、胰岛素分泌和痛觉感知等生理过程。它们是多不饱和脂肪酸（PUFA）的代谢产物，包括花生四烯酸、二十碳五烯酸和二十二碳六烯酸，由哺乳动物细胞表达的12-脂氧合酶（LOX）和环氧化物水解酶（EH）形成。在此，我们鉴定出原核生物黄色粘球菌产生的十种HXs和TrXs，其中六种是新的，即HXB、HXD、HXE、TrXB、TrXD和TrXE。通过在大肠杆菌中表达黄色粘球菌12-LOX或11-LOX（有无EH），我们成功地将PUFAs生物转化为八种HXs（转化率>35%）和TrXs（转化率>10%）。我们确定11-羟基-二十碳四烯酸、HXB、HXB、HXD、TrXB和TrXD为潜在的过氧化物酶体增殖物激活受体-γ部分激动剂。这些发现可能有助于基于脂质介质的生理学研究和药物开发。
