Engineered Production of Short-Chain Acyl-Coenzyme A Esters in Saccharomyces cerevisiae,ACS Synthetic Biology

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Engineered Production of Short-Chain Acyl-Coenzyme A Esters in Saccharomyces cerevisiae
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2018-03-02 00:00:00 , DOI: 10.1021/acssynbio.7b00466
Nicolas Krink-Koutsoubelis _{1,

2} , Anne C. Loechner _{1,

2} , Anna Lechner ₃ , Hannes Link _{1,

2} , Charles M. Denby _{3,

4} , Bastian Vögeli _{1,

2} , Tobias J. Erb _{1,

2} , Satoshi Yuzawa _{3,

4} , Tadas Jakociunas ₅ , Leonard Katz ₆ , Michael K. Jensen ₅ , Victor Sourjik _{1,

2} , Jay D. Keasling _{3,

4,

5,

6,

7}

Affiliation

Short-chain acyl-coenzyme A esters serve as intermediate compounds in fatty acid biosynthesis, and the production of polyketides, biopolymers and other value-added chemicals. S. cerevisiae is a model organism that has been utilized for the biosynthesis of such biologically and economically valuable compounds. However, its limited repertoire of short-chain acyl-CoAs effectively prevents its application as a production host for a plethora of natural products. Therefore, we introduced biosynthetic metabolic pathways to five different acyl-CoA esters into S. cerevisiae. Our engineered strains provide the following acyl-CoAs: propionyl-CoA, methylmalonyl-CoA, n-butyryl-CoA, isovaleryl-CoA and n-hexanoyl-CoA. We established a yeast-specific metabolite extraction protocol to determine the intracellular acyl-CoA concentrations in the engineered strains. Propionyl-CoA was produced at 4–9 μM; methylmalonyl-CoA at 0.5 μM; and isovaleryl-CoA, n-butyryl-CoA, and n-hexanoyl-CoA at 6 μM each. The acyl-CoAs produced in this study are common building blocks of secondary metabolites and will enable the engineered production of a variety of natural products in S. cerevisiae. By providing this toolbox of acyl-CoA producing strains, we have laid the foundation to explore S. cerevisiae as a heterologous production host for novel secondary metabolites.

中文翻译：

酿酒酵母中短链酰基辅酶A酯的工程化生产

短链酰基辅酶A酯是脂肪酸生物合成以及聚酮化合物，生物聚合物和其他增值化学品生产中的中间化合物。酿酒酵母是一种模型生物，已被用于生物合成这种具有生物学和经济价值的化合物。但是，其短链酰基辅酶A的种类有限，有效地阻止了其作为大量天然产物的生产宿主的应用。因此，我们将生物合成代谢途径引入了酿酒酵母中的五种不同的酰基辅酶A酯。我们的工程菌株提供以下酰基CoA：丙酰基CoA，甲基丙二酰基CoA，正丁酰基CoA，异戊酰基CoA和n-己酰基-CoA。我们建立了酵母特异性代谢物提取方案，以确定工程菌株中细胞内酰基辅酶A的浓度。丙酰辅酶A的产量为4–9μM；0.5μM的甲基丙二酰辅酶A; 分别为6μM的异戊酰基-CoA，正丁酰基-CoA和正己酰基-CoA。这项研究中产生的酰基辅酶A是常见的次级代谢产物，可通过工程化方法生产酿酒酵母中的多种天然产物。通过提供此酰基辅酶A产生菌株的工具箱，我们为探索酿酒酵母作为新型次生代谢产物的异源生产宿主奠定了基础。

更新日期：2018-03-02

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