Promoter engineering enables precise metabolic regulation towards efficientβ-elemene production in Ogataea polymorpha

作     者：Min Ye Jiaoqi Gao Jingjing Li Wei Yu Fan Bai Yongjin J.Zhou 

作者机构：Division of BiotechnologyDalian Institute of Chemical PhysicsChinese Academy of Sciences457 Zhongshan RoadDalian116023PR China CAS Key Laboratory of Separation Science for Analytical ChemistryDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian116023PR China Dalian Key Laboratory of Energy BiotechnologyDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian116023PR China University of Chinese Academy of SciencesBeijing100049PR China 

出 版 物：《Synthetic and Systems Biotechnology》 (合成和系统生物技术（英文）)

年 卷 期：2024年第9卷第2期

页      面：234-241页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 08[工学] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种] 

基　　金：This research was supported by the National Key Research and Development Project(2023YFC3503900) Liaoning Distinguished Scholar Program(2023JH6/100500001) 

主　　题：Promoter library Growth phase-dependent promoters Promoter engineering Precise metabolic regulation Ogataea polymorpha 

摘      要：Precisely controlling gene expression is beneficial for optimizing biosynthetic pathways for improving the ***,promoters in nonconventional yeasts such as Ogataea polymorpha are always limited,which results in incompatible gene ***,we expanded the promoter library in *** based on transcriptional data,among which 13 constitutive promoters had the strengths ranging from 0–55%of PGAP,the commonly used strong constitutive promoter,and 2 were growth phase-dependent ***,2 hybrid growth phase-dependent promoters were constructed and characterized,which had 2-fold higher ***,promoter engineering was applied to precisely regulate cellular metabolism for efficient production ofβ-*** glyceraldehyde-3-phosphate dehydrogenase gene GAP was downregulated to drive more flux into pentose phosphate pathway(PPP)and then to enhance the supply of acetyl-CoA by using phosphoketolase-phosphotransacetylase(PK-PTA)*** with the phase-dependent expression of synthase module(ERG20∼LsLTC2 fusion),the highest titer of 5.24 g/L with a yield of 0.037 g/(g glucose)was achieved in strain YY150U under fed-batch fermentation in shake *** work characterized and engineered a series of promoters,that can be used to fine-tune genes for constructing efficient yeast cell factories.