Creation of Bioorthogonal Redox Systems Depending on Nicotinamide Flucytosine Dinucleotide
Ji, Debin1,2; Wang, Lei1,2; Hou, Shuhua1,2; Liu, Wujun1,3; Wang, Jinxia1; Wang, Qian1,3; Zhao, Zongbao K.1,3
刊名journal of the american chemical society
2011-12-28
卷号133期号:51页码:20857-20862
ISSN号待补充
通讯作者赵宗保
产权排序1,1
中文摘要creation of bioorthogonal redox systems depending on nicotinamide flucytosine dinucleotide
英文摘要many enzymes catalyzing biological redox chemistry depend on the omnipresent cofactor, nicotinamide adenine dinucleotide (nad). nad is also involved in various nonredox processes. it remains challenging to disconnect one particular nad-dependent reaction from all others. here we present a bioorthogonal system that catalyzes the oxidative decarboxylation of l-malate with a dedicated abiotic cofactor, nicotinamide flucytosine dinucleotide (nfcd). by screening the multisite saturated mutagenesis libraries of the nad-dependent malic enzyme (me), we identified the mutant me-l310r/q401c, which showed excellent activity with nfcd, yet marginal activity with nad. we found that another synthetic cofactor, nicotinamide cytosine dinucleotide (ncd), also displayed similar activity with the me mutants. inspired by these observations, we mutated d-lactate dehydrogenase (dldh) and malate dehydrogenase (mdh) to dldh-v152r and mdh-l6r, respectively, and both mutants showed fully active with nfcd. when coupled with dldh-v152r, me-l310r/q401c required only a catalytic amount of nfcd to convert l-malate. our results opened the window to engineer bioorthogonal redox systems for a wide variety of applications in systems biology and synthetic biology.
学科主题物理化学
WOS标题词science & technology ; physical sciences
类目[WOS]chemistry, multidisciplinary
研究领域[WOS]chemistry
关键词[WOS]escherichia-coli ; directed evolution ; nad(+) transporter ; xylose reductase ; small molecules ; swiss-model ; specificity ; enzymes ; binding ; protein
收录类别SCI
语种英语
WOS记录号WOS:000298571600037
公开日期2012-07-09
内容类型期刊论文
源URL[http://159.226.238.44/handle/321008/115835]  
专题大连化学物理研究所_中国科学院大连化学物理研究所
作者单位1.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
2.Chinese Acad Sci, Grad Univ, Beijing 100039, Peoples R China
3.Dalian Natl Lab Clean Energy, Dalian 116023, Peoples R China
推荐引用方式
GB/T 7714
Ji, Debin,Wang, Lei,Hou, Shuhua,et al. Creation of Bioorthogonal Redox Systems Depending on Nicotinamide Flucytosine Dinucleotide[J]. journal of the american chemical society,2011,133(51):20857-20862.
APA Ji, Debin.,Wang, Lei.,Hou, Shuhua.,Liu, Wujun.,Wang, Jinxia.,...&Zhao, Zongbao K..(2011).Creation of Bioorthogonal Redox Systems Depending on Nicotinamide Flucytosine Dinucleotide.journal of the american chemical society,133(51),20857-20862.
MLA Ji, Debin,et al."Creation of Bioorthogonal Redox Systems Depending on Nicotinamide Flucytosine Dinucleotide".journal of the american chemical society 133.51(2011):20857-20862.
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