主要研究内容：
1.微生物代谢工程：利用生物质等可再生资源，通过微生物细胞工厂的转化，生产重要的材料和化学品，建立绿色可持续的材料和化学品供给路线。主要开展化学品生物合成新途径的设计和构建、代谢关键酶的催化机理研究和性能改造、廉价碳源生物转化途径的设计和构建、细菌代谢调控机制解析、底盘细胞性能优化等研究工作。
2.细菌抗逆性机制：分析细菌在不同环境胁迫下的响应过程，解析细菌对外界环境信号的传感机制和信号传递通路，阐明相关功能基因在逆境胁迫下的作用。主要开展细菌二组分系统、核糖开关、信使小分子等不同层面的调控因子的传感及相互作用机制，调控因子对下游基因的调节机制以及基因功能等研究工作。
标志性成果：
1. 在生物基材料和化学品方面，针对生物合成中的瓶颈问题，在廉价碳源利用、转化效率提升、产品性能优化等方面取得了突出成果，建立了制备3-羟基丙酸和丁三醇等重要化学品的生物合成系统，实现了廉价可再生原料的高效生物转化，完成了生物合成技术的中试应用验证；同时提出了多功能蛋白拆分的代谢工程新思路，建立了细胞内碳代谢流再分配调控策略和生物基高分子性能调控策略等。以该成果为基础获基金委优秀青年基金资助。
2. 在细菌抗逆性机制方面，以重要的模式微生物——沙门氏菌和大肠杆菌为研究对象，针对其在生长过程中受到的环境胁迫，在转录调控、转录后调控、翻译后调控等不同层面系统分析了重要功能基因的表达调控机制：阐明了沙门氏菌通过二组分系统PhoPQ和调控蛋白SlyA整合细胞内外不同信号，进而管理毒力基因表达的复杂调节系统；首次报道了响应氨基酸外小分子信号的转录翻译偶联调控机制；首次建立了感应Mn2+的核糖开关模型；发现了对数期细菌酸耐受性新机制。相关成果发表于Nat Commun、PNAS、JBC等杂志。
发表论文：（*通讯作者，†并列第一作者）
Chen JH†, Guo LK†, Zhang Y, Zhao MH, Li MJ, Zhao Z, Qi QS, Xian M, Liu M*, Zhao G*. Metabolic engineering of Escherichia coli for bioproducion of (R)-3-hydroxybutyric acid through a three-pronged approach. J Agric Food Chem, 2024, DOI: 10.1021/acs.jafc.4c04123.
Jiang B, Liu JZ, Wang JN, Zhao G*, Zhao Z. Adaptive evolution for the efficient production of high-quality d-lactic acid using engineered Klebsiella pneumoniae. Microorganisms, 2024, 12:1167.
76 Microorganisms-乳酸进化-Zhao-2024.pdf
Liu XT†, Li LQ†, Zhao G*, Xiong P*. Optimization strategies for CO2 biological fixation. Biotechnol Adv, 2024, 73, 108364.
75 Biotechnol Adv-CO2 fixation review-2024.pdf
Sui XY, Wang JC, Zhao ZQ, Liu B, Liu MM, Liu M, Shi C, Feng XJ, Fu YX, Shi DY, Li SY, Qi QS, Xian M, Zhao G*. Phenolic compounds induce ferroptosis-like death by promoting hydroxyl radical generation in Fenton reaction. Commun Biol, 2024, 7: 199.
74 Commun Biol-PG toxicity-Sui-2024.pdf
Guo LK†, Liu M†, Bi YJ, Qi QS, Xian M, Zhao G*. Using a synthetic machinery to improve carbon yield with acetylphosphate as the core. Nat Commun, 2023, 14: 5286.
72 Nat Commun-SCTPK-Guo-2023.pdf
Liu M†, Huo MT†, Guo LK, Fu YX, Xian M, Qi QS, Liu W*, Zhao G*. Lysine acetylation decreases enzyme activity and protein level of Escherichia coli lactate dehydrogenase. Eng Microbiol, 2022, 2(4): 100045.
69 Eng Microb-LdhA acetylation-Liu-2022.pdf
Liu M†, Huo MT†, Liu CS, Guo LK, Ding YM, Ma QJ, Qi QS, Xian M*, Zhao G*. Lysine acetylation of Escherichia coli lactate dehydrogenase regulates enzyme activity and lactate synthesis. Front Bioeng Biotechnol, 2022, 10: 966062.
68 Front Bioeng-LdhA acetylation-Liu-2022.pdf
Zhao Z, Xu Y, Jiang B, Qi QS, Tang YJ, Xian M, Wang JC*, Zhao G*. Systematic identification of CpxRA-regulated genes and their roles in Escherichia coli stress response. mSystems, 2022, 7(5): e00419-22.
70 mSystems-Cpx regulon-Zhao-2022.pdf
Liu M†, Guo LK†, Fu YX, Huo MT, Qi QS, Zhao G*. Bacterial protein acetylation and its role in cellular physiology and metabolic regulation. Biotechnol Adv, 2021, 53: 107842.
66 Biotech Adv-acetylation review-LiuMin-2021.pdf
Wang JC†, Sui XY†, Ding YM, Fu YX, Feng XJ, Liu M, Zhang YM, Xian M*, Zhao G*. A fast and robust iterative genome-editing method based on a rock-paper-scissors strategy. Nucleic Acids Res, 2020, 49(2): e12.
65 NAR-RPS CRISPR system-Wang-2020.pdf
Liu XT, Feng XJ, Ding YM, Gao WJ, Xian M, Wang JC*, Zhao G*. Characterization and directed evolution of propionyl-CoA carboxylase and its application in succinate biosynthetic pathway with two CO2 fixation reactions. Metab Eng, 2020, 62:42-50.
62 Metab Eng-PCC directed evolution-Liu-2020.pdf
Sun SM, Ding YM, Liu M, Xian M, Zhao G*. Comparison of glucose, acetate and ethanol as carbon resource for production of poly(3-hydroxybutyrate) and other acetyl-CoA derivatives. Front Bioeng Biotechnol, 2020, 8:33.
61 Front Bioeng Biotech-ethanol utilization-Sun-2020.pdf
Zhou YF, Ding YM, Gao WJ, Wang JC, Liu XT, Xian M, Feng XJ*, Zhao G*. Biosynthesis of acetylacetone inspired by its biodegradation. Biotechnol Biofuels, 2020, 13:88.
60 Biotech Biofuels-acetylacetone-Zhou-2020.pdf
Xu Y†, Zhao Z†, Tong WH, Ding YM, Liu B, Shi YX, Wang JC, Sun SM, Liu M, Wang YH, Qi QS, Xian M*, Zhao G*. An acid-tolerance response system protecting exponentially growing Escherichia coli. Nat Commun, 2020, 11:1496.
59 NC-acid tolerance-Xu-2020.pdf
Liu M, Fu YX, Gao WJ, Xian M*, Zhao G*. Highly efficient biosynthesis of hypoxanthine in Escherichia coli and transcriptome-based analysis of the purine metabolism. ACS Synth Biol, 2020, 9(3):525-535.
57 ACSsynbio-hypoxathine-Liu-2020.pdf
Zhao Z, Xian M, Liu M*, Zhao G*. Biochemical routes for uptake and conversion of xylose by microorganisms. Biotechnol Biofuels, 2020, 13:21.
56 Biotechnol Biofuels-xylose review-2020.pdf
Feng XJ, Gao WJ, Zhou YF, Zhao ZQ, Liu XT, Han XJ, Xian M*, Zhao G*. Coupled biosynthesis and esterification of 1,2,4-butanetriol to simplify its separation from fermentation broth. Eng Life Sci, 2019, 19:444-451.
53 Eng Life Sci-BT esterification-Feng-2019.pdf
Wang YH, Xian M, Feng XJ, Liu M*, Zhao G*. Biosynthesis of ethylene glycol from d-xylose in recombinant Escherichia coli. Bioengineered, 2018, 9(1): 233-241.
50 Bioengineered-ethylene glycol-Wang-2018.pdf
Liu M, Ding YM, Xian M*, Zhao G*. Metabolic engineering of a xylose pathways for biotechnological production of glycolate in Escherichia coli. Microb Cell Fact, 2018, 17:51.
Feng XJ†, Jiang LQ†, Han XJ, Liu XT, Zhao ZQ, Liu HZ, Xian M*, Zhao G*. Production of D-lactate from glucose using Klebsiella pneumoniae mutants. Microb Cell Fact, 2017, 16: 209.
46 MCF-D-lactate from glucose-Feng-2017.pdf
Liu H, Cheng T, Zou HB*, Zhang HB, Xu X, Sun C, Aboulnaga E, Cheng ZK, Zhao G*, Xian M*. High titer mevalonate fermentation and its feeding as a building block for isoprenoids (isoprene and sabinene) production in engineered Escherichia coli. Process Biochem, 2017, 62: 1-9.
Lactama ST， Kuiate JR, Ding YM, Xian M, Liu HZ, Boudjeko T, Feng XJ*, Zhao G*. Enhanced poly(3-hydroxypropionate) production via β-alanine pathway in recombinant Escherichia coli. PLoS One, 2017, 12:e0173150.
44 PLoS One-beta-alanine pathway optimization-2017.pdf
Lactama ST†, Yao L†, Xian M, Liu H, Kuiate JR, Liu HZ, Feng XJ*, Zhao G. A novel autolysis system controlled by magnesium and its application to poly(3-hydroxypropionate) production in engineered Escherichia coli. Bioengineered, 2017, 8(5):594-9.
43 Bioengineered-autolysis-2017.pdf
Liu CS, Ding YM, Xian M, Liu M, Liu HZ, Ma QJ, Zhao G*. Malonyl-CoA pathway: a promising route for 3-hydroxypropionate biosynthesis. Crit Rev Biotechnol, 2017, 37(7):933-41.
42 CritRevBiot-MCR pathway-2017.pdf
Cheng T†, Liu H†, Zou HB*, Cheng NN, Shi MX, Xie CX, Zhao G*, Xian M*. Enzymatic process optimization for the in vitro production of isoprene from mevalonate. Microb Cell Fact, 2017, 16:8.
41 MCF-in vitro enzyme reaction-2017.pdf
Liu M, Ding YM, Chen HL, Zhao Z, Liu HZ, Xian M*, Zhao G*. Improving the production of acetyl-CoA-derived chemicals in Escherichia coli BL21(DE3) through iclR and arcA deletion. BMC Microbiol, 2017, 17:10.
40 BMC Microbiol-iclR-2017.pdf
Tong WH, Xu Y, Xian M, Niu W, Guo JT, Liu HZ*, Zhao G*. Biosynthetic pathway for acrylic acid from glycerol in recombinant Escherichia coli. Appl Mircobiol Biotechnol, 2016, 100(11): 4901-7.
Liu M, Han XP, Xian M, Ding YM, Liu HZ*, Zhao G*. Development of a 3-hydroxypropionate resistant Escherichia coli strain. Bioengineered, 2016, 7(1): 21-7.
36 Bioengineered-acid resistance proteome-2016.pdf
Liu CS, Ding YM, Zhang RB, Liu HZ, Xian M*, Zhao G*. Functional balance between enzymes in malonyl-CoA pathway for 3-hydroxypropionate biosynthesis. Metab Eng, 2016, 34: 104-11.
34 ME-MCR directed evolution-2016.pdf
Liu M, Yao L, Xian M, Ding YM, Liu HZ*, Zhao G*. Deletion of arcA increased the production of acetyl-CoA-derived chemicals in recombinant Escherichia coli. Biotechnol Lett, 2016, 38(1):97-101.
32 BiotechnolLett-arcA-2016.pdf
Liu M, Feng XJ, Ding YM, Zhao G, Liu HZ*, Xian M*. Metabolic engineering of Escherichia coli to improve recombinant protein production. Appl Microbiol Biotechnol, 2015, 99(24):10367-77.
Feng XJ, Xian M, Liu W, Xu C, Zhang HB, Zhao G*. Biosynthesis of poly(3-hydroxypropionate) from glycerol using engineered Klebsiella pneumoniae strain without vitamin B12. Bioengineered, 2015, 6(2):77-81.
30 Bioengineered-glycerol pathway in Kp-2015.pdf
Feng XJ, Ding YM, Xian M, Xu X, Zhang RB, Zhao G*. Production of optically pure D-lactate from glycerol by engineered Klebsiella pneumoniae strain. Bioresour Technol, 2014, 172:269-75.
Wang Q, Yang P, Xian M, Feng L, Wang JM, Zhao G*. Metabolic engineering of Escherichia coli for poly (3-hydroxypropionate) production from glycerol and glucose. Biotechnol Lett, 2014, 36(11):2257-62.
27 BiotechnolLett-beta-alanine pathway-2014.pdf
Gao YQ, Liu CS, Ding YM, Sun C, Zhang RB, Xian M*, Zhao G*. Development of genetically stable Escherichia coli strains for poly(3-hydroxypropionate) production. PLoS One, 2014, 9(5): e97845.
25 PLoSOne-stable strain-2014.pdf
Wang Q, Yang P, Xian M, Liu H, Cao YJ, Yang Y, Zhao G*. Production of block copolymer poly(3-hydroxybutyrate)-block-poly(3-hydroxypropionate) with adjustable structure from inexpensive carbon source. ACS Macro Lett, 2013, 2(11): 996-1000.
23 ACSMacroLett-block copolymer-2013.pdf
Liu CS, Wang Q, Xian M, Ding YM, Zhao G*. Dissection of malonyl-coenzyme A reductase of Chloroflexus aurantiacus results in enzyme activity improvement. PLoS One, 2013, 8(9): e75554.
22 PLoSOne-MCR dissection-2013.pdf
Gao YQ†, Feng XJ†, Xian M, Wang Q, Zhao G*. Inducible cell lysis systems in microbial production of bio-based chemicals. Appl Microbiol Biotechnol, 2013, 97(16): 7121-9.
Wang Q, Yang P, Xian M, Yang Y, Liu CS, Xue YC, Zhao G*. Biosynthesis of Poly(3-hydroxypropionate-co-3-hydroxybutyrate) with fully controllable structures from glycerol. Bioresour Technol, 2013, 142: 741-4.
19 BITE-random copolymer-2013b.pdf
Wang Q, Yang P, Liu CS, Xue YC, Xian M*, Zhao G*. Biosynthesis of poly(3-hydroxypropionate) from glycerol by recombinant Escherichia coli. Bioresour Technol, 2013, 131: 548-51.
18 BITE-glycerol pathway-2013a.pdf
Wang Q, Liu CS, Xian M, Zhang YG, Zhao G*. Biosynthetic pathway for poly(3-hydroxypropionate) in recombinant Escherichia coli. J Microbiol, 2012, 50(4): 693-7.
16 JMicrobiol-MCR pathway-2012.pdf
Zheng YN, Li LL, Liu Q, Yang JM, Wang X, Liu W, Xu X, Liu H, Zhao G*, Xian M*. Optimization of fatty alcohol biosynthesis pathway for selectively enhanced production of C12/14 and C16/18 fatty alcohols in engineered Escherichia coli. Microb Cell Fact, 2012, 11: 65.
17 BiotechBiofuel-Zheng-2012.pdf
Shi Y*, Zhao G, Kong W. Genetic analysis of riboswitch-mediated transcriptional regulation responding to Mn2+ in Salmonella. J Biol Chem, 2014, 289(16): 11353-66. DOI: 10.1074/jbc.M113.517516.
Zhao G†, Kong W†, Weatherspoon N, Clark-Curtiss J, Shi Y*. Mg2+ facilitates leader peptide translation to induce riboswitch-mediated transcription termination. EMBO J, 2011, 30(8): 1485-96. DOI: 10.1038/emboj.2011.66.
Weatherspoon N†, Zhao G†, Kong W, Kong Y, Morigen, Andrews-Polymenis H, McClelland M, Shi Y*. The CpxR/CpxA two-component system upregulates two Tat-dependent peptidoglycan amidases to confer bacterial resistance to antimicrobial peptide protamine. J Biol Chem, 2011, 286(7): 5529-39. DOI: 10.1074/jbc.M110.200352.
Zhao G, Weatherspoon N, Kong W, Curtiss R 3rd, Shi Y*. A dual-signal regulatory circuit activates transcription of a set of divergent operons in Salmonella typhimurium. P Natl Acad Sci USA, 2008, 105(52): 20924-9. DOI: 10.1073/pnas.0807071106.
Feng L, Wang W, Cheng JS, Ren Y, Zhao G, Gao CX, Tang Y, Liu XQ, Han WQ, Peng X, Liu RL and Wang L*. Genome and proteome of long-chain alkane degrading Geobacillus thermodenitrificans NG80-2 isolated from a deep-subsurface oil reservoir. P Natl Acad Sci USA, 2007, 104(13): 5602-7. DOI: 10.1073/pnas.0609650104.
Feng L†, Perepelov AV†, Zhao G†, Shevelev SD, Wang Q, Senchenkova SN, Shashkov AS, Geng YQ, Reeves PR, Knirel YA and Wang L*. Structural and genetic evidence that the Escherichia coli O148 O antigen is the precursor of the Shigella dysenteriae type 1 O antigen and identification of a glucosyltransferase gene. Microbilogy, 2007, 153(1): 139-47. DOI: 10.1099/mic.0.2006/001107-0.
Zhao G, Perepelov AV*, Senchenkova SN, Shashkov AS, Feng L, Li XM, Knirel YA, Wang L. Structural relation of the antigenic polysaccharides of Escherichia coli O40, Shigella dysenteriae type 9, and E. coli K47. Carbohydr Res, 2007, 342(9): 1275-9. DOI: 10.1016/j.carres.2007.03.005.
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