Reassessing acetyl-CoA supply and NADPH availability for mevalonate biosynthesis from glycerol in Escherichia coli,Biotechnology and Bioengineering

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Reassessing acetyl-CoA supply and NADPH availability for mevalonate biosynthesis from glycerol in Escherichia coli
Biotechnology and Bioengineering ( IF 3.5 ) Pub Date : 2022-07-03 , DOI: 10.1002/bit.28167
Yan Wang ₁ , Shenting Zhou ₁ , Runyi Li ₁ , Qian Liu ₁ , Xixi Shao ₁ , Liyan Zhu ₁ , Min-Kyoung Kang ₂ , Gongyuan Wei ₁ , Seon-Won Kim ₂ , Chonglong Wang ₁

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Mevalonate is an important platform compound for the biosynthesis of isoprenoids. It can be synthesized from acetyl-CoA in the presence of nicotinamide adenine dinucleotide phosphate (NADPH) by the introduced mvaES operon in Escherichia coli. The influences of E. coli hosts, acetyl-CoA supply, and NADPH availability were assessed and engineered to improve the production titer and yield of mevalonate from glycerol. As a result, E. coli DH5α was found to be the best host with high specific capability and titer of mevalonate from glycerol. Through the engineering of phosphoketolase-phosphotransacetylase (xPK-PTA) bypass and NADPH availability, a final titer of 7.21 g/L with a specific capability of 1.36 g/g dry cell weight was gained in flask culture. Our work could offer new information to metabolically engineer the mevalonate pathway for the efficient production of isoprenoids.

中文翻译：

重新评估大肠杆菌中甘油合成甲羟戊酸的乙酰辅酶 A 供应和 NADPH 可用性

甲羟戊酸是类异戊二烯生物合成的重要平台化合物。它可以通过在大肠杆菌中引入的mvaES操纵子在烟酰胺腺嘌呤二核苷酸磷酸 (NADPH) 存在下由乙酰辅酶 A 合成。评估和设计了大肠杆菌宿主、乙酰辅酶 A 供应和 NADPH 可用性的影响，以提高甘油甲羟戊酸的生产效价和产量。结果，大肠杆菌DH5α被发现是具有高特异性能力和来自甘油的甲羟戊酸滴度的最佳宿主。通过磷酸酮醇酶-磷酸转乙酰酶 (xPK-PTA) 旁路工程和 NADPH 可用性，在烧瓶培养中获得了 7.21 g/L 的最终滴度和 1.36 g/g 干细胞重量的比能力。我们的工作可以为代谢工程甲羟戊酸途径提供新的信息，以有效生产类异戊二烯。

更新日期：2022-07-03

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