Discovery and Engineering of a Microbial Double-Oxygenating Lipoxygenase for Synthesis of Dihydroxy Fatty Acids as Specialized Proresolving Mediators
- 주제(키워드) enzyme engineering , molecular modeling , microbial double-oxygenating lipoxygenase , biotransformation , specialized proresolving mediators
- 주제(기타) Chemistry, Multidisciplinary
- 주제(기타) Green & Sustainable Science & Technology
- 주제(기타) Engineering, Chemical
- 설명문(일반) [Lee, Jin; An, Jung-Ung; Kim, Tae-Hun; Oh, Deok-Kun] Konkuk Univ, Dept Biosci & Biotechnol, Seoul 05029, South Korea; [An, Jung-Ung] Korea Res Inst Biosci & Biotechnol KRIBB, Synthet Biol & Bioengn Res Ctr, Daejeon 34141, South Korea; [Ko, Yoon-Joo] Seoul Natl Univ, Natl Coll Cr Interuniv Res Facil NCIRF, Seoul 08826, South Korea; [Park, Jin-Byung] Ewha Womans Univ, Dept Food Sci & Engn, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 AMER CHEMICAL SOC
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000174683
- 본문언어 영어
- Published As http://dx.doi.org/10.1021/acssuschemeng.0c04793
초록/요약
Specialized proresolving mediators (SPMs), such as resolvins and maresins, resolve inflammation and protect against infection at trace amounts generated by neutrophils and macrophages in humans. Thus, SPMs have been leading compounds in treatment of inflammation and infection. These mediators have been synthesized using chemical methods, which have disadvantages such as use of toxic chemical reagents, many (20-30) step reactions, and expensive processes. Here, we first discovered a human SPM-producing microorganism and found a 15-lip-oxygenase (15-LOX) from the microorganism that produces SPMs via double oxygenation from polyunsaturated fatty acids. The 15-LOX was altered to 12-LOX using structure-based engineering. We performed the quantitative biocatalytic synthesis of SPMs by wild-type 15-LOX and engineered 12-LOX. Owing to the high double-oxygenating activities of LOXs, we succeeded in the one-enzyme biotransformation of docosahexaenoic acid and docosapentaenoic acid into the SPM resolvin D5 (RvD5, 7S,17S-dihydroxydocosahexaenoic acid) and RvD5(n-3 DPA) (7S,17S-dihydroxydocosapentaenoic acid) (>40% conversion), respectively, by Escherichia coli expressing wild-type 15-LOX and into the 7S-epimer of maresin (MaR) 1 (7S,14S-dihydroxydocosahexaenoic acid) and 7S-epimer of MaR1(n-3 DPA) (7S,14S-dihydroxydocosapentaenoic acid) (>20% conversion), respectively, by E. coli expressing engineered 12-LOX. Our study contributes to the environmentally friendly synthesis of medicinally important SPMs.
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