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个人信息

博士生导师
研究员
2018年获得“国家杰出青年基金”
Email: syang@sibs.ac.cn
个人网页: http://people.ucas.edu.cn/~yangsheng

研究方向

微生物代谢调控与酶工程研究

杨晟

个人简介

1995年 本科毕业于浙江大学化学工程系生物化学工程专业
2000年 博士毕业于中国科学院上海生物化学研究所
2000-2002 中国科学院上海生命科学研究院生物化学与细胞生物学研究所 助理研究员
2002-2006 中国科学院上海生命科学研究院植物生理生态研究所次生代谢分子调控研究开放实验室 副研究员
2006-2008 中国科学院上海生命科学研究院植物生理生态研究所分子微生物学开放实验室 副主任 研究员
2006-2010 上海市药学会抗生素专业委员会 委员
2007-2015 中国微生物学会酶工程专业委员会 副主任委员
2010-2012 上海市生物工程学会 副秘书长;
2011-2012 中国科学院天津工业生物技术研究所(筹)学术委员会 委员
2002年至今 中国微生物学会酶工程专业委员会 委员
2011年至今 工业酶国家工程实验室技术委员会 委员
2011年至今 中国生物工程学会工业与环境生物技术专业委员会 副主任委员
2011年至今 中国微生物学会分子微生物学与生物工程专业委员会 委员
2016年至今 中国微生物学会分子微生物学与生物工程专业委员会 副主任委员
2011年至今 中国科学院研究生院工程硕士(生物工程领域)专业学位教育指导委员会 委员
2012年至今 《工业微生物》《生物工程学报》编委
2015-2020 中国生物工程学会 理事
2006年至今 中国科学院上海生命科学研究院湖州工业生物技术中心 主任;
2008年至今 上海工业生物技术研发中心 主任;中国科学院合成生物学重点实验室 研究员
2016年至今 中国科学院微生物系统工程重点实验室 学术委员会 委员
2016年至今 中国生物工程学会氨基酸专业委员会 副主任委员

研究工作

重组生物催化剂作为人工系统的适配性研究是生物催化剂工程领域的一个重要方向和关键科学问题。
本实验室聚焦于该科学问题十余年,先后发现基因组探矿适配大肠杆菌表达系统;Red重组可有效修复Cas9造成的大肠杆菌DNA双链断口;Cpf1(而非Cas9)与谷氨酸棒杆菌兼容。这些发现被用于多样性酶制剂库的构建与重要工业微生物的基因组编辑,创建高产萜类工程细胞与高效生物统合工艺体系并证实适配机制分别为前体途径间的能量与还原力耦合及菌间丁酸产生与回用耦合。以上工作为蛋白质重组表达、基因组编辑工具开发、萜类代谢工程与人工菌群设计提供了新的思路与策略,在医药中间体、氨基酸与燃料乙醇等领域获二十余种应用,经济效益显著。
招收的研究生将深入研究重要底盘微生物的CRISPR-Cas适配原理,发展基因组编辑工具以解析高产机理并创制理想生物催化剂。

主要成果

1 磷酸甲基赤藓糖醇途径与甲羟戊酸途径的协同效应
所有萜类物质均需通过磷酸甲基赤藓糖醇(methylerythritol phosphate, MEP)途径或甲羟戊酸(mevalonate, MVA)途径合成,以往的萜类代谢工程均只优化其中一条途径。申请人在大肠杆菌进行了数十轮十余靶点的基因工程操作,同时优化两条途径,双途径较单途径菌株的异戊二烯得率高3倍以上,突破单途径得率的理论上限,较之前报道最高的发酵单位还要提高一个数量级。同位素流量分析与途径特异性抑制剂及甲羟戊酸添加实验证明还原力和ATP互补在双途径协同中起到了关键作用。并且这一协同效应亦能提高其他萜类如番茄红素的生产强度,表明这一策略在提高微生物萜类合成能力上具普适性。相关研究结果发表于Metabolic Engineering上。

2 梭菌戊糖代谢工程
我们将CRISPR/Cas系统首次适配到丙酮丁醇梭菌中,实现了无痕敲除及表达抑制功能,并做微调后用于拜氏梭菌和嗜纤梭菌。秸秆糖液尚需由预处理生物质添加纤维素酶糖化后才能作为发酵原料。统合生物工艺(Consolidated Bioprocessing , CBP)的策略是将糖化和发酵整合到一个生物过程中,从而省去外源添加纤维素酶带来的较高成本。课题组选取,运用TargeTron和以上CRISPR/Cas技术,将嗜纤梭菌与拜氏梭菌人工双梭菌系统分产酸、酸回用、木糖利用和还原力供应4个模块进行代谢工程改造(图1)。第一步中断了嗜纤梭菌的乙酸激酶和乳酸脱氢酶并过表达丁酸激酶,将其代谢流推向丁酸;第二步用CRISPRi抑制了嗜纤梭菌的氢酶转录,以减少释放氢气损失的还原力,用于产醇;第三步过表达拜氏梭菌的辅酶A转移酶加强回用嗜纤梭菌所产丁酸;第四步中断拜氏梭菌的木糖阻遏子和过表达木糖转运体增强木糖内运和代谢。这四步改造将人工双梭菌转化玉米芯产溶剂的速度大为提升,通过中间补加玉米芯的方法,可将溶剂终浓度提升到22 g/L,达到用淀粉糖培养基同样的水平。相关研究结果发表于Metabolic Engineering上。

获奖情况:
DuPont Young Professor Award (杜邦青年教授奖 2006)
国务院政府特殊津贴 (2010)
中国科学院院地合作奖 科技类先进个人一等奖 (2010)
《载体固定化酶---原理、应用和设计》(与袁中一研究员共同主译) 中国石油和化学工业优秀出版物奖(图书奖) 一等奖 (2010)
上海市优秀学科带头人 (2014)
中国产学研合作创新成果奖 (2014)
中国专利优秀奖(2015)
Novozymes Innovation Award (诺维信创新奖 2015)
上海市科技进步一等奖 (2015)
伦世仪教育基金杰出青年(2016)
中国科学院科技促进发展奖(2016)

    He Huang, Xin Song, Sheng Yang*2019 Development of a RecE/T-Assisted CRISPR-Cas9 Toolbox for Lactobacillus. Biotechnology journal. doi: 10.1002/biot.201800690.

    Qi Li, Francois M. Seys, Nigel P. Minton, Junjie Yang, Yu Jiang, Weihong Jiang, Sheng Yang*(2019)CRISPR-Cas9(D10A) nickase-assisted base editing in solvent producer Clostridium beijerinckii. Biotechnol Bioeng. Doi: 10.1002/bit.26949

    Zhiqiang Wen, Ledesma-Amaro, Rodrigo; Jianping Lin*, Yu Jiang, Sheng Yang*(2019)Improved n-butanol production from Clostridium cellulovorans by integrated metabolic and evolutionary engineering. Appl Environ Microbiol. Doi: 10.1128/AEM.02560-18

    Xinyun Jing, Bingran Xie, Longxian Chen, Niubing Zhang, Yiyi Jiang, Hang Qin, Hongbing Wang, Pei Hao*, Sheng Yang* , Xuan Li*(2018)Implementation of the CRISPR-Cas13a system in fission yeast and its repurposing for precise RNA editing. Nucleic Acids Res. Doi :10.1093/nar/gky433

    Bingbing Sun, Junjie Yang, Sheng Yang*, Richard D. Ye*, Daijie Chen,*; Yu Jiang*(2018)A CRISPR-Cpf1-Assisted Non-Homologous End Joining Genome Editing System of Mycobacterium smegmatis. Biotechnology journal. 13 (9)

    Xin Wang, Junjie Yang, Sheng Yang*, Yu Jiang*(2018)Unraveling the genetic basis of fast L-arabinose consumption on top of recombinant xylose-fermenting Saccharomyces cerevisiae. Biotechnol Bioeng. Doi:10.1002/bit.26827

    Jun Sun, Qingzhuo Wang, Yu Jiang, Zhiqiang Wen, Lirong Yang, Jianping Wu* and Sheng Yang*(2018)Genome editing and transcriptional repression in Pseudomonas putida KT2440 via the type II CRISPR system. Microb Cell Fact. 17:41

    Xin Song, He Huang, Zhi-Qiang Xiong, Lianzhong Ai*, Sheng Yang* (2017) CRISPR-Cas9D10A Nickase-Assisted Genome Editing in Lactobacillus casei. Appl. Environ. Microbiol. doi: 10.1128/AEM.01259-17

    Qi Liu, Yu Jiang, Lei Shao, Ping Yang, Bingbing Sun,Sheng Yang*, and Daijie Chen* (2017) CRISPR/Cas9-based efficient genome editing in Staphylococcus aureus. Acta Biochim Biophys Sin. doi: 10.1093/abbs/gmx074

    Xiaoshu Xu, Chao Wang, Jun Chen, and Sheng Yang* (2017)Streptomyces virginiae PPDC is a new type of phenylpyruvate decarboxylase composed of two subunits. ACS Chemical Biology 2017; doi:10.1021/acschembio.7b00307

    Yu Jiang, Fenghui Qian, Junjie Yang, Yingmiao Liu, Feng Dong, Chongmao Xu, Bingbing Sun, Biao Chen, Xiaoshu Xu, Yan Li, Renxiao Wang, Sheng Yang* (2017) CRISPR-Cpf1 -assisted genome editing of Corynebacterium glutamicum Nature Communications.doi:10.1038/ncomms15179

    Shuliang Gao, Yangyang Tong, Li Zhu, Ge Mei, Zhang Yian, Daijie Chen, Yu Jiang, Sheng Yang* (2017) Iterative integration of multiple-copy pathway genes in Yarrowia lipolytica for heterologous β-carotene production. Metabolic Engineering. 41:192-201

    Zhiqiang Wen, Nigel P. Minton, Ying Zhang, Qi Li, Jinle Liu, c, Yu Jiang, Sheng Yang*(2017)Enhanced solvent production by metabolic engineering of a twin-clostridial consortium. Metabolic Engineering.39:38-48

    Junjie Yang and Sheng Yang* (2016)Comparative analysis of Corynebacterium glutamicum genomes: a new perspective for the industrial production of amino acids. BMC Genomics . 18(1):940

    Yu Jiang, Rongsheng Tao, Zhengquan Shen, Liangdong Sun, Fuyun Zhu, Sheng Yang*(2016)Enzymatic Production of Glutathione by Bifunctional γ-Glutamylcysteine Synthetase/Glutathione Synthetase Coupled with In Vitro Acetate Kinase-Based ATP Generation. Appl Biochem Biotechnol.180(7) 1446-1455

    Yingmiao Liu,Junzhi Wang, Chongmao Xu,Yong Chen, Junjie YangDong Liu, Huanqing Niu, Yu Jiang, Sheng Yang*, Hanjie Ying*(2016)Efficient multi-enzyme-catalyzed CDP-choline production drivenby an ATP donor module. Appl Microbiol Biotechnol.101:1409-1417

    Yingmiao Liu, Junjie Yang, Yu Jiang, Sheng Yang* (2016). Complete genome sequence of nucleoside producing strain Corynebacterium stationis ATCC 6872. Journal of Biotechnology,225(10):57–58

    Shuliang Gao, Yangyang Tong, Zhiqiang Wen, Li Zhu, Mei Ge, Daijie Chen*, Yu Jiang*, Sheng Yang* (2016) Multiplex gene editing of the Yarrowia lipolytica genome using the CRISPR-Cas9 system. Journal of Industrial Microbiology & Biotechnology . 43(8)1085–1093

    Yu Jiang Rongsheng Tao , Sheng Yang* (2016) Tailor-made biocatalysts enzymes for the fine chemical industry in China. Biotechnol Journal. 11,1121–1123

    Qi Li, Jun Chen, Nigel P. Minton, Ying Zhang, Zhiqiang Wen, Jinle Liu, Haifeng Yang, Zhe Zeng, Xiaodan Ren, Junjie Yang, Yang Gu, Weihong Jiang, Yu Jiang, Sheng Yang* (2016) CRISPR-based genome editing and expression control systems in Clostridium acetobutylicum and Clostridium beijerinckii. Biotechnology Journal. 11(7):961-72

    Chen Yang, Xiang Gao, Yu Jiang, Bingbing Sun, Fang Gao, Sheng Yang*(2016)Synergy between methylerythritol phosphate pathway and mevalonate pathway for isoprene production in Escherichia coli, Metabolic Engineering, 2016, 37:79–91

    Xiaoshu Xu, Jun Chen, Qingzhuo Wang, Chunlan Duan, Yan Li, Renxiao Wang,Sheng Yang*(2016) Mutagenesis of Key Residues in the Binding Center of l-Aspartate-b-Semialdehyde Dehydrogenase from Escherichia coli Enhances Utilization of the Cofactor NAD(H), ChemBioChem.17:56-64

    Gang Xu, Yu Jiang, Rongsheng Tao, Shengfeng Wang, Hongyu Zeng, Sheng Yang* (2015)A recyclable biotransformation system for l-2-aminobutyric acid production based on immobilized enzyme technology. Biotechnology Letters. 38(1):123-9

    Yu Jiang, Biao Chen, Chunlan Duan, Bingbing Sun, Junjie Yang, and Sheng Yang* (2015)Multigene Editing in the Escherichia coli Genome via the CRISPR-Cas9 System. Appl. Environ. Microbiol. 81:2506-14

    Ning Zhang, Lijun Shao, Yu Jiang, Yang Gu, Qi Li, Jinle Liu, Weihong Jiang, Sheng Yang* (2015) I-SceI-mediated scarless gene modification via allelic exchange in Clostridium. Journal Microbial Methods. 108:49-60

    Yu Jiang, Jinle Liu, Yunliu Yang, Weihong Jiang, Sheng Yang* (2014) Current status and prospects of industrial bio-production of n-butanol in China, Biotechnology Advances. 33:1493-1501

    Junjie Yang, Bingbing Sun, He Huang, Yu Jiang, Liuyang Diao, Biao Chen, Chongmao Xua,Xin Wang, Jinle Liu, Weihong Jiang, Sheng Yang* (2014) High-efficiency Scarless Genetic Modification in Escherichia coli Using lambda-Red Recombination and I-SceI Cleavage. Appl. Environ. Microbiol. 80(13):3826-34

    Rongsheng Tao, Yu Jiang, Fuyun Zhu, Sheng Yang* (2014) A one-pot system for production ofL-2-aminobutyric acid from L-threonine by L-threonine deaminase and a NADH regeneration system based on L-leucine dehydrogenase and formate dehydrogenase. Biotechnology Letters 36(4):835-41

    Liuyang Diao, Yingmiao Liu, Fenghui Qian, Junjie Yang, Yu Jiang, Sheng Yang* (2013)Construction of fast xylose-fermenting yeast based on industrial ethanol-producing diploid Saccharomyces cerevisiaeby rational design and adaptive evolution. BMC Biotechnology 13:110

    Zhilin Li, Han Xiao, Weihong Jiang, Yu Jiang*, Sheng Yang* (2013) Improvement of butanol production from xylose mother liquor by engineering xylose metabolic pathway in Clostridium acetobutylicum EA 2018. Applied Biochemistry and Biotechnology. 171(3):555-68

    Han Xiao, Zhilin Li, Yu Jiang, Yunliu Yang, Weihong Jiang, Yang Gu*, Sheng Yang* (2012) Metabolic engineering of D-xylose pathway in Clostridium beijerinckii to optimize solvent production from xylose mother liquid. Metabolic Engineering 14: 565-578

    Han Xiao, Yang Gu, Yuanyuan Ning, Yunliu Yang, W.J. Mitchell, Weihong Jiang*, Sheng Yang* (2011) Confirmation and elimination of xylose-metabolic bottlenecks in glucose-PTS-deficient Clostridium acetobutylicum to realize simultaneous utilization of glucose, xylose and arabinose. Appl. Environ. Microbiol 77:7886-7895

    Zhoutong Sun, Yuanyuan Ning, Lixia Liu, Yingmiao Liu, Bingbing Sun, Weihong Jiang, Chen Yang and Sheng Yang* (2011) Metabolic engineering of the L-phenylalanine pathway in Escherichia coli for the production of S- or R-mandelic acid. Microbial Cell Factories. 10:71 Highly Accessed

    Shiyuan Hu, Huajun Zheng, Yang Gu, Jingbo Zhao, Weiwen Zhang, Yunliu Yang, Shengyue Wang, Guoping Zhao, Sheng Yang*, Weihong Jiang* (2011) Comparative genomic and transcriptomic analysis revealed genetic characteristics related to solvent formation and xylose utilization in Clostridium acetobutylicum EA 2018. BMC Genomics 12(1):93.

    Li Zhu, Rongsheng Tao, Yi Wang, Yu Jiang, Xin Lin, Yunliu Yang, Huabao Zheng, Weihong Jiang, Sheng Yang* (2011) Removal of L-alanine from the production of L-2-aminobutyric acid by introduction of alanine racemase and D-amino acid oxidase. Appl Microbiol Biotechnol. 90:903-910

    Dalong Zhang, Fuyun Zhu, Wenchao Fan, Rongsheng Tao, Hong Yu, Yunliu Yang, Weihong Jiang, Sheng Yang* (2011) Gradually accumulating beneficial mutations to improve the thermostability of N-carbamoyl-D-amino acid amidohydrolase by step-wise evolution. Appl. Microbiol. Biotechnol. 90:1361-1371.

    Cong REN, Yang GU, Shiyuan HU,Yan WU,Pan WANG, Chen YANG, Sheng YANG*, Weihong JIANG* (2010) Identification and inactivation of pleiotropic regulator CcpA to eliminate glucose repression of xylose utilization in Clostridium acetobutylicum. Metabolic Engineering 12(5): 446-454

    Jian LI, Jingbo ZHAO, Meng ZHAO, Yunliu YANG, Weihong JIANG, Sheng YANG* (2010)Screening and Characterization of Butanol Tolerant Microorganisms. Letters in Applied Microbiology 50: 373-9

    Yang GU, Jian LI, Lei ZHANG, Jun CHEN, Lixia NIU, Yunliu YANG, Sheng YANG*, Weihong JIANG* (2009) Improvement of xylose utilization in Clostridium acetobutylicum via expression of the talA gene encoding transaldolase from Escherichia coli. Journal of Biotechnology 143:284-287

    Yu JIANG, Chongmao XU, Feng DONG, Yunliu YANG, Weihong JIANG*, Sheng YANG* (2009) Disruption of the acetoacetate decarboxylase gene in solvent-producing Clostridium acetobutylicum increases the butanol ratio. Metabolic Engineering 11: 284-91

    Yang GU, Shiyuan HU, Jun CHEN, Lijun SHAO, Huiqi HE, Yunliu YANG, Sheng YANG*, Weihong JIANG*(2009). Ammonium acetate enhances solvent production by Clostridium acetobutylicum EA 2018 using cassava as a fermentation medium. J Ind Microbiol Biotechnol, 36:1225-1232.

    Junjie YANG, Weihong JIANG, Sheng YANG* (2009). mazF as a counter-selectable marker for unmarked genetic modification of Pichia pastoris. FEMS Yeast Research. 9(4): 600-9

    Hong YU, Jian LI, Dalong ZHANG, Yunliu YANG, Weihong JIANG, Sheng YANG* (2009). Improving the thermostability of N-carbamyl-D-amino acid amidohydrolase by error-prone PCR. Appl. Microbiol. Biotechnol. 82(2): 279-85

    Lijun SHAO, Shiyuan HU, Yi YANG, Yang GU, Jun CHEN, Yunliu YANG, Weihong JIANG*, Sheng YANG* (2007) Targeted gene disruption by use of a group II intron (targetron) vector in Clostridium acetobutylicum. Cell Research. 17: 963-5

    Huabao ZHENG, Jun CHEN, Liuli SU, Yuhua ZHAO, Yunliu YANG, Sheng YANG* and Weihong JIANG (2007) One-step purification and immobilization of GL-7-ACA acylase by affinity resins. Enzymatic and Microbial Technology. 41: 474-9.

    Jingang WANG, Qing ZHANG, He HUANG, Zhongyi YUAN, Dafu DING, Sheng YANG*, Weihong JIANG (2007) Increasing Synthetic Performance of Penicillin G Acylase from Bacillus megaterium by Site-directed Mutagenesis. Applied Microbiology and Biotechnology. 74: 1023-30.

    Huabao ZHENG, Xiaolan WANG, Jun CHEN, Ke ZHU, Yuhua ZHAO, Yunliu YANG, Sheng YANG*, Weihong JIANG (2006) Expression, purification and immobilization of His-tagged D-amino acid oxidase of Trigonopsis variabilis in Pichia pastoris, Applied Microbiology and Biotechnology, 70(6): 683-9

    Tianfan CHENG, Maolin CHEN, Huabao ZHENG, Jingang WANG, Sheng YANG*, Weihong JIANG (2006) Expression and Purification of Penicillin G Acylase Enzymes from Four Different Micro-organisms, and a Comparative Evaluation of Their Synthesis/Hydrolysis Ratios for Cephalexin. Protein Expression and Purification, 46, 107-13

    Yu XIA, Wei CHEN, Sheng YANG*, Xiaoyan FU, Hao ZHANG*, Xiaolin DING (2005) Construction of an integrative food-grade expression system for Bacillus subtilis. Food Research International. 38(3), 251-6

    Li PENG, Zhinan XU*, Xiangming FANG, Fang WANG, Sheng YANG*, Peilin CEN (2004) Preferential codons enhancing the expression level of human β-defensin-2 in recombinant Escherichia coli. Protein and Peptide Letters 11(4), 339-44

    Zheng ZHOU, Aihui ZHANG, Jingru WANG, Maolin CHEN, Renbao LI, Sheng YANG*, Zhongyi YUAN * (2003) Improving the specific synthetic activity of a penicillin G acylase using DNA family shuffling. ACTA BIOCHIMICA et BIOPHYSICA SINICA

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