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Exploring engineering strategies that enhance de novo production of exotic cyclopropane fatty acids in Saccharomyces cerevisiae
Biotechnology Journal ( IF 3.2 ) Pub Date : 2024-02-26 , DOI: 10.1002/biot.202300694
Wei Jiang 1, 2, 3 , Huadong Peng 2, 3 , Lizhong He 1 , Rodrigo Lesma‐Amaro 2, 3 , Victoria S. Haritos 1
Affiliation  

Cycloalkanes have broad applications as specialty fuels, lubricants, and pharmaceuticals but are not currently available from renewable sources, whereas, production of microbial cycloalkanes such as cyclopropane fatty acids (CFA) has bottlenecks. Here, a systematic investigation was undertaken into the biosynthesis of CFA in Saccharomyces cerevisiae heterologously expressing bacterial CFA synthase. The enzyme catalyzes formation of a 3‐membered ring in unsaturated fatty acids. Monounsaturated fatty acids in phospholipids (PL) are the site of CFA synthesis; precursor cis‐Δ9 C16 and C18 fatty acids were enhanced through OLE1 and SAM2 overexpression which enhanced CFA in PL. CFA turnover from PL to storage in triacylglycerols (TAG) was achieved by phospholipase PBL2 overexpression and acyl‐CoA synthase to increase flux to TAG. Consequently, CFA storage as TAG reached 12 mg g−1 DCW, improved 3‐fold over the base strain and >22% of TAG was CFA. Our research improves understanding of cycloalkane biosynthesis in yeast and offers insights into processing of other exotic fatty acids.

中文翻译:

探索增强酿酒酵母中外来环丙烷脂肪酸从头生产的工程策略

环烷烃作为特种燃料、润滑剂和药品具有广泛的应用,但目前无法从可再生来源获得,而环丙烷脂肪酸 (CFA) 等微生物环烷烃的生产存在瓶颈。在此,对 CFA 的生物合成进行了系统研究酿酒酵母异源表达细菌CFA合酶。该酶催化不饱和脂肪酸中三元环的形成。磷脂(PL)中的单不饱和脂肪酸是CFA合成的场所;前体顺式-Δ9 C16 和 C18 脂肪酸通过以下方式得到增强奥莱1SAM2结束表达增强了 PL 中的 CFA。CFA 从 PL 到三酰甘油 (TAG) 中储存的周转是通过磷脂酶实现的PB2过表达和酰基辅酶A合酶可增加 TAG 的流量。因此,作为 TAG 的 CFA 储存量达到 12 mg g−1DCW,比基础菌株提高了 3 倍,并且 > 22% 的 TAG 是 CFA。我们的研究提高了对酵母中环烷烃生物合成的理解,并为其他外来脂肪酸的加工提供了见解。
更新日期:2024-02-26
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