Construction of an Alternative NAD+ De Novo Biosynthesis Pathway,Advanced Science

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Construction of an Alternative NAD+ De Novo Biosynthesis Pathway
Advanced Science ( IF 14.3 ) Pub Date : 2021-03-01 , DOI: 10.1002/advs.202004632
Yong Ding _{1,

2} , Xinli Li _{1,

2} , Geoff P Horsman ₃ , Pengwei Li ₁ , Min Wang _{1,

2} , Jine Li ₁ , Zhilong Zhang _{1,

2} , Weifeng Liu ₁ , Bian Wu _{1,

2} , Yong Tao _{1,

2} , Yihua Chen _{1,

2}

Affiliation

Nicotinamide adenine dinucleotide (NAD⁺) is a life essential molecule involved in versatile biological processes. To date, only two de novo biosynthetic routes to NAD⁺ are described, both of which start from a proteinogenic amino acid and are tightly controlled. Here, a de novo quinolinic acid pathway starting from chorismate, which provides an alternative route (named as the C3N pathway) to NAD⁺ biosynthesis, is established. Significantly, the C3N pathway yields extremely high cellular concentrations of NAD(H) in E. coli. Its utility in cofactor engineering is demonstrated by introducing the four‐gene C3N module to cell factories to achieve higher production of 2,5‐dimethylpyrazine and develop an efficient C3N‐based whole‐cell bioconversion system for preparing chiral amines. The wide distribution and abundance of chorismate in most kingdoms of life implies a general utility of the C3N pathway for modulating cellular levels of NAD(H) in versatile organisms.

中文翻译：

替代 NAD+ 从头生物合成途径的构建

烟酰胺腺嘌呤二核苷酸 (NAD ⁺ ) 是参与多种生物过程的生命必需分子。迄今为止，仅描述了两种 NAD ⁺的从头生物合成途径，这两种途径均从蛋白质氨基酸开始并受到严格控制。^{在此，建立了从分支酸开始的从头喹啉酸途径，为NAD +}生物合成提供了一条替代途径（称为C3N途径）。值得注意的是，C3N 途径在大肠杆菌中产生极高的细胞浓度的 NAD(H) 。通过将四基因 C3N 模块引入细胞工厂，以实现更高的 2,5-二甲基吡嗪产量，并开发一种高效的基于 C3N 的全细胞生物转化系统来制备手性胺，证明了其在辅因子工程中的实用性。分支酸在大多数生命王国中的广泛分布和丰富意味着 C3N 途径在调节多种生物体中 NAD(H) 的细胞水平方面具有普遍用途。

更新日期：2021-05-05

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