能源生物技术

　　生物质是未来生产液体燃料和化学品的重要原料，但其利用尚面临预处理效率低、转化产物选择性低、资源利用度低等问题。研究以生物转化技术为核心，将生物质转化为长碳链燃料分子和生物基化学品所涉及的基础科学和工程技术问题。主要内容包括：

　　1） 酵母油脂技术
　　2） 生物质综合利用技术

代表性论文：

1. Huang QT#, Kamal R#, Shen HW, Lu HB, Song JY, Chu YD, Xue C*, Zhao ZK*. “Pilot-scale conversion of corn stover into lipids by the red yeast Rhodosporidium toruloides” J. Environ. Chem. Eng. 2022, 10, 108858.

2. Kamal R, Huang QT, Li Q, Chu YD, Yu X, Limtong S, Xue S, Zhao ZK*. “Conversion of Arthrospira platensis biomass into microbial lipids by the oleaginous yeast Cryptococcus curvatus” ACS Sust. Chem. Eng. 2021, 9(33), 11011–11021.

3. Liu HF, Han JY, Huang QT, Shen HW, Lei LJ, Huang ZP, Zhang ZX, Zhao ZK*, Wang F*. “Catalytic hydrodeoxygenation of methyl stearate and microbial lipids to diesel-range alkanes over Pd/HPA-SiO₂ catalysts” Ind. Eng. Chem. Res. 2020, 59(39), 17440–17450.

4. Dai XZ, Shen HW, Li Q, Rasool K, Wang Q, Yu X, Wang L, Bao J, Yu DY*, Zhao ZK* “Microbial lipid production from corn stover by the oleaginous yeast Rhodosporidium toruloides using the PreSSLP process” Energies 2019, 12, 1053.

5. Gong ZW, Shen HW, Yang XB, Wang Q, Xie HB, Zhao ZK*. “Lipid production from corn stover by the oleaginous yeast Cryptococcus curvatus” Biotechnol. Biofuels 2014, 7, 158.

6. Shen HW, Gong ZW, Yang XB, Jin GJ, Bai FW*, Zhao ZK*. “Kinetics of continuous cultivation of the oleaginous yeast Rhodosporidium toruloides” J. Biotechnol. 2013, 168(1), 85–89.

7. Xie HB*, Shen HW, Gong ZW, Wang Q, Zhao ZK*, Bai FW. “Enzymatic hydrolysates of corn stover pretreated by the N-methylpyrrolidone/ionic liquids solution for microbial lipid production” Green Chem. 2012, 14(4), 1202–1210.　

8. Hu CM, Wu SG, Wang Q, Jin GJ, Shen HW, Zhao ZK*. “Simultaneous utilization of glucose and xylose for lipid production by Trichosporon cutaneum” Biotechnol. Biofuels 2011, 4, 25.　

合成生物学

　　充分利用产油酵母等真核微生物独特的代谢可塑性和抗逆性，对高效转化复杂生物质原料至关重要。研究产油酵母生长和代谢调控的分子基础及遗传操作体系，构建系列平台菌株，创制先进的“脂质细胞工厂”。主要内容包括：

　　1） 脂质合成底盘细胞研究
　　2） 人工合成体系创制

代表性论文：

1. Zhang Y, Zhang SF, Chu YD, Zhang Q, Zhou RH, Yu D, Wang S, Lyu LT, Xu GW, Zhao ZK*. “Genetic manipulation of the interconversion between diacylglycerols and triacylglycerols in Rhodosporidium toruloides” Front. Bioeng. Biotechnol. 2022, 10, 1034972.

2. Lyu LT*, Chu YD, Zhang SF, Zhang Y, Huang QT, Wang S, Zhao ZK*. “Engineering the oleaginous yeast Rhodosporidium toruloides for improved resistance against inhibitors in biomass hydrolysates” Front. Bioeng. Biotechnol. 2021, 9, 768934.

3. Jiao X, Zhang Y, Liu XJ, Zhang Q, Zhang SF*, Zhao ZK*. “Developing a CRISPR/Cas9 system for genome editing in the basidiomycetous yeast Rhodosporidium toruloides” Biotechnol. J. 2019, 14, 1900036.

4. Wang YN, Zhang SF*, Zhu ZW, Shen HW, Lin XP, Jin X, Jiao X, Zhao ZK*. “Systems analysis of phosphate-limitation induced lipid accumulation by the oleaginous yeast Rhodosporidium toruloides” Biotechnol. Biofuels 2018, 11, 148.

5. Zhu ZW, Zhou YJ, Krivoruchko A, Grininger M, Zhao ZK*, Nielsen J*. “Expanding the product ortfolio of fungal type I fatty acid synthases” Nat. Chem. Biol. 2017, 13(4), 360–362. (Cover Article)

6. Guo J, Zhou YJ, Hillwig ML, Shen Y, Yang L, Wang YJ, Zhang XN, Liu WJ, Peters RJ*, Chen XY, Zhao ZK*, Huang LQ*. “CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts”Proc. Natl. Acad. Sci. USA 2013, 110(29), 12108–12113.

7. Zhu ZW, Zhang SF, Liu HW, Shen HW, Lin XP, Yang F, Zhou YJ, Jin GJ, Ye ML, Zou HF*, Zhao ZK*. “A multi-omic map of the lipid-producing yeast Rhodosporidium toruloides” Nat. Commun. 2012, 3, 1112. 　Data

8. Zhou YJ, Gao W, Rong QX, Jin GJ, Chu HY, Liu WJ, Yang W, Zhu ZW, Li GH, Zhu GF, Huang LQ*, Zhao ZK*. “Modular pathway engineering of diterpenoid synthases and the mevalonic acid pathway for miltiradiene production” J. Am. Chem. Soc. 2012, 134(6), 3234–3241.

化学生物学

　　研究利用外源化学物质，通过非天然辅酶介导，调控胞内能量传递及能量代谢过程，揭示其详细作用机制，拓展对物质转化及生命现象化学本质的科学认识，构建可控、可设计的生物体系。主要内容包括：

       1） 非天然辅酶及探针合成　 
       2） 能量传递与代谢研究

代表性论文：

1. Li Q, Guo XJ, Wang XY, Wang JT, Wan L, Xue HZ, Zhao ZK*. “Creation of cytochrome P450 catalysis depending on a non-natural cofactor for fatty acid hydroxylation” J. Energy Chem. 2023, 79, 31–36.

2. Wang XY, Feng YB, Guo XJ, Wang Q, Ning SY, Li Q, Wang JT, Wang L, Zhao ZK*. “Creating enzymes and self-sufficient cells for biosynthesis of the non-natural cofactor nicotinamide cytosine dinucleotide” Nat. Commun. 2021, 12(1), 2116.

3. Guo XJ, Liu YX, Wang Q, Wang XY, Li Q, Liu WJ, Zhao ZK*. “Non-natural cofactor and formate-driven reductive carboxylation of pyruvate” Angew. Chem. Int. Ed. 2020, 59(8), 3143–3146.

4. Liu YX, Feng YB, Wang L, Guo XJ, Liu WJ, Li Q, Wang XY, Xue S*, Zhao ZK*. “Structural insights into phosphite dehydrogenase variants favoring a non-natural redox cofactor” ACS Catal. 2019, 9(3), 1883–1887.

5. Wang L, Ji DB, Liu YX, Wang Q, Wang XY, Zhou YJ, Zhang YX, Liu WJ*, Zhao ZK*. “Synthetic Cofactor-Linked Metabolic Circuits for selective energy transfer” ACS Catal. 2017, 7(3), 1977–1983.

6. Zhang YX, Pan YB, Liu WJ, Zhou YJ, Wang KY, Wang L, Sohail M, Ye ML, Zou HF*, Zhao ZK*. “In vivo protein allylation to capture protein methylation candidates” Chem. Commun. 2016, 52(40), 6689–6692.

7. Zhou YJ, Yang W, Wang L, Zhu ZW, Zhang SF, Zhao ZK*. “Engineering NAD+ availability for Escherichia coli whole-cell biocatalysis: a case study for dihydroxyacetone production” Microbial Cell Factories 2013, 12, 103.

8. Ji DB, Wang L, Hou SH, Liu WJ, Wang JX, Wang Q, Zhao ZK*. “Creation of bioorthogonal redox systems depending on nicotinamide flucytosine dinucleotide” J. Am. Chem. Soc. 2011, 133(51), 20857–20862.