于浩然 科创青年卓越人才
博士，研究员，浙大“百人计划”研究员
职务：合成生物所 PI
研究方向：合成生物学，蛋白质工程，生物催化
邮箱:yuhaoran@zju.edu.cn
地址：杭州市萧山区建设三路733号浙江大学杭州国际科创中心
个人简介：
于浩然博士近年来一直从事开发理性设计方法用于酶分子的改造研究，并在此领域做出了国际领先的原创性贡献。具体而言，针对限制酶分子工业化应用的稳定性、活性、立体选择性等性质，创新性地提出了一系列可用于指导酶分子理性设计的思路，并成功应用于转酮酶、荧光素酶、肠激酶、胰蛋白酶、苏氨酸醛缩酶、脂肪酶等多种具有工业应用价值的酶分子改造中。这些研究为酶分子的高效理性设计改造提供了理论依据与实践方法，加深了对蛋白质结构与功能之间关系的认识，推动了生物催化剂在工业实践中的应用。相关成果以第一作者在PNAS（IF=9.412，2篇），Biotechnology Advances (IF=10.744，1篇),The FEBS Journal (IF=4.392，1篇), Scientific Report (IF=3.998，1篇)等杂志发表学术论文8篇，并作为共同作者在ACS Catalysis (IF=12.35，1篇)、ChemCatChem (IF=4.853，1篇)等杂志发表学术论文6篇。此外，基于相关成果应邀在Elsevier出版的著名电子图书《酶学方法》中撰写章节。总体上，累计发表SCI论文14篇，授权国家发明专利1项，SCI数据库引用240次，他引216次，其中第一作者论文SCI他引共200次。另外，主持浙江大学与伦敦大学学院国际合作项目1项、浙江大学曹光彪高科技发展基金资助项目1项、参与英国工程和物理科学研究委员会（The Engineering and Physical Sciences Research Council）资助的重点项目3项，任英国皇家化学学会准会员（Associate Member）。
工作研究项目：
课题组在蛋白质工程领域从事酶分子的智能化计算机设计工作，具体研究方向包括：
1、基于分子动力学的酶分子设计研究；
2、基于机器学习的酶分子设计研究；
3、基于非天然氨基酸引入的酶分子设计研究。
发表论文：
(1) Haoran Yu#, Yanjie Liu#, LiujieHuo, Xinya Liang, Guangbo Kang, He Huang*. Soluble expression of active recombinant firefly Luciferase in Escherichia coli. Journal of Pure and Applied Microbiology. Vol.7, NO. Special Edition, Nov 2013. ISSN 0973-7510.
(2) Haoran Yu, He Huang*. Engineering proteins for thermostability through rigidifying flexible sites. Biotechnology Advances, 2014, 32 (2):308-315.
(3) Haoran Yu#, Yang Zhao#, Chao Guo, Yiru Gan, He Huang*. The role of proline substitutions within flexible regions on thermostability of luciferase. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2015, 1854 (1): 65-72.
(4) Chao Guo, Ye Liu, Haoran Yu, Kun Du, Yiru Gan, He Huang*. A novel strategy for thermostability improvement of trypsin based on N-glycosylation within the Ω-Loop region. Journal of microbiology and biotechnology, 2016, 26 (7):1163-1172.
(5) Haoran Yu, Yihan Yan, Cheng Zhang, Paul A. Dalby*. Two strategies to engineer flexible loops for improved enzyme thermostability. Scientific Reports 7, Article number: 41212 (2017) doi:10.1038/srep41212.
(6) Cheng Zhang, Maariyah Samad, Haoran Yu, Nesrine Chakroun, David Hilton, and Paul A. Dalby*. Computational-design to reduce conformational flexibility and aggregation rates of an antibody Fab fragment. Molecular pharmaceutics, 2018, 15 (8): 3079-3092.
(7) Lin Liu, Haoran Yu, Kun Du, Zhiyan Wang, Yiru Gan, He Huang*. Enhanced trypsin thermostability in Pichia pastoris through truncating the flexible region. Microbial cell factories, 2018, 17 (1): 165-174.
(8) Haoran Yu, Paul A. Dalby*. Coupled molecular dynamics mediate long and short-range epistasis between mutations that affect stability and aggregation kinetics. Proceedings of the National Academy of Sciences, 2018, 115 (47) : E11043-E11052.
(9) Haoran Yu, Paul A. Dalby*. Exploiting correlated molecular-dynamics networks to counteract enzyme activity-stability trade-off. Proceedings of the National Academy of Sciences, 2018, 115 (52): E12192- E12200.
(10) Haoran Yu, Roberto Icken Hernandez Lopez, David Steadman, Daniel Mendez-Sanchez, Sally Higson, Armando Cazares-Korner, Tom D. Sheppard, John M Ward, Helen C Hailes, Paul A Dalby*. Engineering transketolase to accept both unnatural donor and acceptor substrates and produce α-hydroxyketones. The FEBS Journal, 2020, doi:10.1111/febs.15108.
(11) Haoran Yu, Paul A Dalby*. A beginner's guide to molecular dynamics simulations and the identification of cross-correlation networks for enzyme engineering. Methods in Enzymology, 2020.
(12) Jinling Xu, Haisheng Zhou*, Haoran Yu, Tong Deng, Ziyuan Wang, Hongyu Zhang, Jianping Wu, Lirong Yang*. Computational design of highly stable and soluble alcohol dehydrogenase for NADPH regeneration. Bioresour. Bioprocess, 2021, 8, 12.
(13) Wenlong Zheng, Haoran Yu, Sai Fang, Kaitong Chen, Zhe Wang, Xiuli Cheng, Gang Xu*, Lirong Yang, and Jianping Wu*. Directed Evolution of l-Threonine Aldolase for the Diastereoselective Synthesis of β-Hydroxy-α-amino Acids. ACS Catalysis, 2021, 11, 6, 3198–3205
(14) Zhonglang Yu, Haoran Yu, Haibin Tang, Zhe Wang, Jianping Wu, Lirong Yang, Gang Xu*. Site‐specifically Incorporate Non‐Canonical Amino Acids into Pseudomonas alcaligenes Lipase to Hydrolyze L‐menthol propionate among the Eight Isomers. ChemCatChem, 2021, DOI: 10.1002/cctc.202100358
专利成果：
1. 一种萤火虫荧光素酶及其编码基因及获取方法; 黄鹤，于浩然，王玥，肖天雄; NO. CN103409380B
