Constructing a synthetic pathway for acetylcoenzyme A from one-carbon through enzyme design
Lu, Xiaoyun1; Liu, Yuwan1; Yang, Yiqun1,2; Wang, Shanshan3; Wang, Qian1,2; Wang, Xiya4; Yan, Zhihui1; Cheng, Jian1; Liu, Cui1; Yang, Xue1,2; Luo, Hao1,2; Yang, Sheng1; Gou, Junran1; Ye, Luzhen1; Lu, Lina1; Zhang, Zhidan1; Guo, Yu2,3,5; Nie, Yan3; Lin, Jianping1; Li, Sheng3; Tian, Chaoguang1; Cai, Tao1; Zhuo, Bingzhao6; Ma, Hongwu1; Wang, Wen6; Ma, Yanhe1; Liu, Yongjun4; Li, Yin7; Jiang, Huifeng1
AbstractAcetyl-CoA is a fundamental metabolite for all life on Earth, and is also a key starting point for the biosynthesis of a variety of industrial chemicals and natural products. Here we design and construct a Synthetic Acetyl-CoA (SACA) pathway by repurposing glycolaldehyde synthase and acetyl-phosphate synthase. First, we design and engineer glycolaldehyde synthase to improve catalytic activity more than 70-fold, to condense two molecules of formaldehyde into one glycolaldehyde. Second, we repurpose a phosphoketolase to convert glycolaldehyde into acetyl-phosphate. We demonstrated the feasibility of the SACA pathway in vitro, achieving a carbon yield similar to 50%, and confirmed the SACA pathway by C-13-labeled metabolites. Finally, the SACA pathway was verified by cell growth using glycolaldehyde, formaldehyde and methanol as supplemental carbon source. The SACA pathway is proved to be the shortest, ATP-independent, carbon-conserving and oxygen-insensitive pathway for acetylCoA biosynthesis, opening possibilities for producing acetyl-CoA-derived chemicals from one-carbon resources in the future.
Indexed BySCI
Funding ProjectNational Natural Science Foundation of China[21773138]
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000462288800009
Original Document TypeArticle
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Cited Times:39[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Corresponding AuthorLiu, Yongjun; Li, Yin; Jiang, Huifeng
Affiliation1.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Key Lab Syst Microbial Biotechnol, Tianjin 300308, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.ShanghaiTech Univ, Shanghai Inst Adv & Immunochem Studies, Shanghai 201210, Peoples R China
4.Shandong Univ, Sch Chem & Chem Engn, Jinan 250100, Shandong, Peoples R China
5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
6.Northwestern Polytech Univ, Ctr Ecol & Environm Sci, Xian 710072, Shaanxi, Peoples R China
7.Chinese Acad Sci, Inst Microbiol, Key Lab Microbial Physiol & Metab Engn, State Key Lab Microbial Resources, Beijing 100101, Peoples R China
Recommended Citation
GB/T 7714
Lu, Xiaoyun,Liu, Yuwan,Yang, Yiqun,et al. Constructing a synthetic pathway for acetylcoenzyme A from one-carbon through enzyme design[J]. NATURE COMMUNICATIONS,2019,10.
APA Lu, Xiaoyun.,Liu, Yuwan.,Yang, Yiqun.,Wang, Shanshan.,Wang, Qian.,...&Jiang, Huifeng.(2019).Constructing a synthetic pathway for acetylcoenzyme A from one-carbon through enzyme design.NATURE COMMUNICATIONS,10.
MLA Lu, Xiaoyun,et al."Constructing a synthetic pathway for acetylcoenzyme A from one-carbon through enzyme design".NATURE COMMUNICATIONS 10(2019).
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