Constructing a synthetic pathway for acetylcoenzyme A from one-carbon through enzyme design

doi:10.1038/s41467-019-09095-z

KMS > 免疫化学研究所 > 特聘教授组 > Roger D. Kornberg组

	Constructing a synthetic pathway for acetylcoenzyme A from one-carbon through enzyme design
	Lu, Xiaoyun 1; Liu, Yuwan 1; Yang, Yiqun 1,2; Wang, Shanshan3 ; Wang, Qian 1,2; Wang, Xiya 4; Yan, Zhihui 1; Cheng, Jian 1; Liu, Cui 1; Yang, Xue 1,2; Luo, Hao 1,2; Yang, Sheng 1; Gou, Junran 1; Ye, Luzhen 1; Lu, Lina 1; Zhang, Zhidan 1; Guo, Yu2,3,5 ; Nie, Yan3 ; Lin, Jianping 1; Li, Sheng3 ; Tian, Chaoguang 1; Cai, Tao 1; Zhuo, Bingzhao 6; Ma, Hongwu 1; Wang, Wen 6; Ma, Yanhe 1; Liu, Yongjun 4; Li, Yin 7; Jiang, Huifeng 1
	2019-03-26
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
卷号	10
发表状态	已发表
DOI	10.1038/s41467-019-09095-z
摘要	Acetyl-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.
收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China[21773138]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000462288800009
出版者	NATURE PUBLISHING GROUP
WOS关键词	THIAMINE-DIPHOSPHATE ; MICROBIAL-PRODUCTION ; ESCHERICHIA-COLI ; MECHANISM ; PROTEIN ; ACTIVATION ; ENABLES ; ACID
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/30632
专题	免疫化学研究所_特聘教授组_结构生物化学实验室国际事务处生命科学与技术学院_博士生
通讯作者	Liu, Yongjun; Li, Yin; Jiang, Huifeng
作者单位	1.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
推荐引用方式 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).