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产油酵母粘红酵母的代谢工程改造用于三乙酸内酯的过量生产。

Metabolic engineering of oleaginous yeast Rhodotorula toruloides for overproduction of triacetic acid lactone.

机构信息

Department of Chemical and Biomolecular Engineering, US Department of Energy Center for Bioenergy and Bioproducts Innovation (CABBI), Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

Department of Chemical Engineering, University of Massachusetts-Lowell, Lowell, Massachusetts, USA.

出版信息

Biotechnol Bioeng. 2022 Sep;119(9):2529-2540. doi: 10.1002/bit.28159. Epub 2022 Jun 23.

Abstract

The plant-sourced polyketide triacetic acid lactone (TAL) has been recognized as a promising platform chemical for the biorefinery industry. However, its practical application was rather limited due to low natural abundance and inefficient cell factories for biosynthesis. Here, we report the metabolic engineering of oleaginous yeast Rhodotorula toruloides for TAL overproduction. We first introduced a 2-pyrone synthase gene from Gerbera hybrida (GhPS) into R. toruloides and investigated the effects of different carbon sources on TAL production. We then systematically employed a variety of metabolic engineering strategies to increase the flux of acetyl-CoA by enhancing its biosynthetic pathways and disrupting its competing pathways. We found that overexpression of ATP-citrate lyase (ACL1) improved TAL production by 45% compared to the GhPS overexpressing strain, and additional overexpression of acetyl-CoA carboxylase (ACC1) further increased TAL production by 29%. Finally, we characterized the resulting strain I12-ACL1-ACC1 using fed-batch bioreactor fermentation in glucose or oilcane juice medium with acetate supplementation and achieved a titer of 28 or 23 g/L TAL, respectively. This study demonstrates that R. toruloides is a promising host for the production of TAL and other acetyl-CoA-derived polyketides from low-cost carbon sources.

摘要

植物源聚酮三乙酸内酯(TAL)已被认为是生物炼制工业有前途的平台化学品。然而,由于其天然丰度低和生物合成的细胞工厂效率低下,其实际应用受到限制。在这里,我们报告了产油酵母罗伦隐球酵母(Rhodotorula toruloides)用于 TAL 过度生产的代谢工程。我们首先从杂种天人菊(Gerbera hybrida)中引入了一个 2-吡喃酮合酶基因(GhPS)到罗伦隐球酵母中,并研究了不同碳源对 TAL 生产的影响。然后,我们系统地采用了各种代谢工程策略,通过增强其生物合成途径和破坏其竞争途径来增加乙酰辅酶 A 的通量。我们发现,与过表达 GhPS 的菌株相比,过表达三磷酸腺苷柠檬酸裂解酶(ACL1)将 TAL 产量提高了 45%,而额外过表达乙酰辅酶 A 羧化酶(ACC1)进一步将 TAL 产量提高了 29%。最后,我们使用葡萄糖或甘蔗汁培养基并添加乙酸进行分批补料生物反应器发酵,对产生的菌株 I12-ACL1-ACC1 进行了表征,分别达到了 28 或 23 g/L 的 TAL 产量。这项研究表明,罗伦隐球酵母是一种很有前途的生产 TAL 和其他乙酰辅酶 A 衍生聚酮类化合物的宿主,可以从低成本碳源中生产。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8592/9540541/dd0fbf1b10e2/BIT-119-2529-g004.jpg

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