Yang, Yang - University of California Santa Barbara - Department of Chemistry and Biochemistry

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Yang, Yang Assistant Professor 收藏完善纠错
University of California Santa Barbara Department of Chemistry and Biochemistry
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个人简介

Education B.S. Chemistry, Peking University (2011) Ph.D. Organic Chemistry, Massachusetts Institute of Technology (2016). Advisor: Prof. Stephen Buchwald Miller Postdoctoral Fellow, University of California, Berkeley (2018). Advisor: Prof. Jeffrey Long NIH Postdoctoral Fellow, California Institute of Technology (2020). Advisor: Prof. Frances Arnold Service 2024-present: editorial board member, Tetrahedron 2024-present: editorial board member, Tetrahedron Letters 2024-present: early career advisory board member, Organic Chemistry Frontiers 2022-present: advisory board member, Tetrahedron Chem 2022-present: youth editorial board member, Green Synthesis and Catalysis Awards and Honors 2024 Amgen Young Investigator Award 2024 American Chemical Society Division of Organic Chemistry Young Investigator 2024 Stanley and Leslie Parsons Award in Biochemistry 2024 Sloan Research Fellowship 2024 Bürgenstock JSP Fellowship 2024 CAPA Distinguished Junior Faculty Award 2023 David & Lucile Packard Fellowship in Science and Engineering 2023 Army Research Office Young Investigator Award 2023 Thieme Chemistry Journals Award 2022 NIH Maximizing Investigators' Research Award (MIRA) 2022 NSF CAREER Award 2022 ACS Herman Frasch Foundation Agricultural Chemistry Grantee 2022 ACS Petroleum Research Fund New Doctoral Investigator Award 2022 UCSB Faculty Career Development Award 2021 UCSB Regent’s Junior Faculty Fellowship Award 2018-2020 NIH Ruth L. Kirschstein Postdoctoral Fellowship 2016-2018 Miller Postdoctoral Fellowship 2016 Outstanding Self-Financed Chinese Students Award 2015 MIT Chemistry K. Barry Sharpless Travel Award 2011-2012 MIT Moore Fellowship 2011 Undergraduate Research and Scholarly Achievement Award 2010 Ko-Guan Leo Scholarship 2010 Hui-Chun Qin and Tsung-Dao Lee Undergraduate Research Fellowship 2009 National Scholarship of China 2008 National Scholarship of China 2008 Canon Freshman Scholarship

研究领域

Enzymes are capable of catalyzing some of the most challenging reactions such as nitrogen fixation and methane oxidation under exceptionally mild conditions. Nonetheless, research to fully unlock enzyme’s immense potential for synthetic applications is still in infancy. By integrating chemistry, biology and artificial intelligence, the Yang laboratory is developing novel biocatalytic strategies to tackle daunting challenges in synthesis, catalysis and biomolecular engineering. First, we are addressing long-standing problems in asymmetric catalysis by taking advantage of the intimate enzyme-substrate interaction that can be easily tuned via directed evolution. Second, by synergistically coupling small-molecule catalysis and biocatalysis, we are advancing novel enzymatic processes that are both new-to-biology and new-to-chemistry. Third, we are developing artificial intelligence and automation tools to accelerate the development of customized biocatalysts and to understand enzyme structure-activity relationships. Using an interdisciplinary approach combining synthetic chemistry, synthetic biology, , computational chemistry and computational biology, we reprogram and reinvent nature’s biosynthetic machineries to access reaction space well beyond the native biochemical landscape. Collectively, these efforts will provide insight into fundamental enzymology and reactivity patterns, allowing for the rapid assembly of small and macromolecules of biomedical as well as materials importance. Metalloredox Radical Biocatalysis 40-50% natural proteins are metalloproteins. By leveraging the unique redox property of first-row transition-metal cofactors spanning a wide potential window, we repurpose and evolve natural metalloenzymes to catalyze unnatural free radical reactions in a stereocontrolled fashion. Our group is the first to coin and implement the general concept of “metalloredox radical biocatalysis” to impose stereocontrol over fleeting radical intermediates. Using metalloredox radical biocatalysis, we advanced a collection of atom transfer-type free radical reactions, whose asymmetric catalysis has long eluded synthetic organic chemists. Pyridoxal Radical Biocatalysis Pyridoxal 5’-phosphate (PLP) enzymes are powerful biocatalysts responsible for the construction and destruction of amino acids in natural metabolism. By converting natural two-electron PLP enzymes to catalyze single electron processes, we develop pyridoxal radical biocatalysis to enable the stereoselective synthesis of a range of valuable non-canonical amino acids (ncAAs), including those possessing multiple contiguous stereocenters that are difficult to prepare by other means. Our group is the first to design and implement “synergistic photoredox-pyridoxal radical biocatalysis” as a general strategy for convergent ncAA synthesis without protecting groups through a radical mechanism. Machine Learning-Guided Enzyme Design and Enzyme Engineering We apply the state-of-the-art machine learning (ML) methods to de novo enzyme design. Using our methods, we generate novel protein sequences with various applications. Integrating sequence, structural and evolutionary information of enzymes, we are also developing next-generation machine learning-guided directed evolution to speed up enzyme engineering.

近期论文

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“Artificial Boron Enzymes“ Xiao-Wang Chen, Zhiyu Bo, and Yang Yang*, Nature Chemical Biology 2024, 20, 1106–1107 . “Machine learning-guided co-optimization of fitness and diversity facilitates combinatorial library design in enzyme engineering” Kerr Ding†, Michael Chin†, Yunlong Zhao†, Binh Khanh Mai, Wei Huang, Huanan Wang, Peng Liu*, Yang Yang* and Yunan Luo*, Nature Communications 2024, 15, 6392. “Dehydration in Water. Solid-Supported Lipases as Green Catalysts for Esterification“ Rohan M. Thomas, Monica Lopez-Lemus, Krithika Ganesh, David B. Obbard, Ganesh Sambasivam, Yang Yang, and Bruce H. Lipshutz*, Green Chemistry 2024, 26, 9320–9329. “Threonine Aldolase-Catalyzed Enantioselective α-Alkylation of Amino Acids through Unconventional Photoinduced Radical Initiation“ Tian-Ci Wang, Zheng Zhang, Guodong Rao, Jiedong Li, Josephine Shirah, R. David Britt, Qilei Zhu* and Yang Yang*, Journal of the American Chemical Society 2024, 146, 22476–22484. “Generative Enzyme Design Guided by Functionally Important Sites and Small-Molecule Substrates“ Zhenqiao Song, Yunlong Zhao, Wenxian Shi, Wengong Jin, Yang Yang* and Lei Li*, International Conference on Machine Learning (ICML) 2024, accepted. “Unnatural Thiamine Radical Enzymes for Photobiocatalytic Asymmetric Alkylation of Benzaldehydes and α-Ketoacids“ Xin Liu, Sheng Xu, Heyu Chen and Yang Yang*, 2024. “Stereoselective amino acid synthesis by photobiocatalytic oxidative coupling“ Tian-Ci Wang, Binh Khanh Mai, Zheng Zhang, Zhiyu Bo, Jiedong Li, Peng Liu* and Yang Yang*, Nature 2024, 629, 98–104. Wenzhen Fu, Yue Fu, Yunlong Zhao, Huanan Wang, Peng Liu* and Yang Yang*, Nature Chemistry 2024, AIP. “Biocatalytic enantioselective C(sp3)–H fluorination enabled by directed evolution of nonheme Fe enzymes“ Liu-Peng Zhao, Binh Khanh Mai, Lida Cheng, Fangqiu Gao, Yunlong Zhao, Rui Guo, Hao Wu, Yongda Zhang, Peng Liu* and Yang Yang*, Nature Synthesis 2024, published onine. ”Stereodivergent Photobiocatalytic Radical Cyclization Through the Repurposing and Directed Evolution of Fatty Acid Photodecarboxylases“ Shuyun Ju, Dian Li, Binh Khanh Mai, Xin Liu, Alec Vallota-Eastman, David L. Valentine, Peng Liu* and Yang Yang*, Nature Chemistry 2024, published online. “Young Career Focus: Assistant Professor Yang Yang (University of California Santa Barbara, USA)“ Synform 2023, 12, A196–A199. “Functional Geometry Guided Protein Sequence and Backbone Structure Co-Design“ Zhenqiao Song, Yunlong Zhao, Wenxian Shi, Yang Yang*, and Lei Li*. Preprint available at arXiv:2310.04343. “Joint Design of Protein Sequence and Structure based on Motifs“ Zhenqiao Song, Yunlong Zhao, Yufei Song, Wenxian Shi, Yang Yang*, and Lei Li*. Preprint available at arXiv:2310.02546. “P450-Catalyzed Atom Transfer Radical Cyclization“ Heyu Chen†, Wenzhen Fu†, Yang Yang*, Methods in Enzymology 2023, 693, 31–49 (invited contribution to the “P450 enzyme” issue). “Practical Biocatalytic Synthesis of Aromatic Nitriles“ Zhiyu Bo and Yang Yang*, Chem Catalysis 2023, 3, 100615 (invited Preview). “Enzymes on Steroids“ Liupeng Zhao, Zhiyu Bo and Yang Yang*, Nature Synthesis 2023, 2, 699–700 (invited News & Views). “Stereoselective Amino Acid Synthesis by Synergistic Photoredox-Pyridoxal Radical Biocatalysis” Lei Cheng, Dian Li, Binh Khanh Mai, Zhiyu Bo, Lida Cheng, Peng Liu* and Yang Yang*, Science 2023, 381, 444–451. “A Biocatalytic Platform for Asymmetric Alkylation of α-Keto Acids by Mining and Engineering of Methyltransferases“ Shuyun Ju, Kaylee P. Kuzelka, Rui Guo, Benjamin Krohn-Hansen, Jianping Wu, Satish K. Nair* and Yang Yang*, Nature Communications 2023, 14, 5704. “Enzyme-Controlled Stereoselective Radical Cyclisation to Arenes Enabled By Metalloredox Biocatalysis“ Wenzhen Fu, Natalia M. Neris, Yue Fu, Yunlong Zhao, Benjamin Krohn-Hansen, Peng Liu* and Yang Yang*, Nature Catalysis 2023, 6, 628–636. “Undirected Biocatalytic Amination of Unactivated C(sp3)-H Bonds” Wenzhen Fu and Yang Yang*, Chem Catalysis 2022, 2, 3287-3289 (invited Preview). “Photoenzymes for Radical C-C Coupling“ Rui Guo, Heyu Chen and Yang Yang*, Nature Catalysis 2022, 5, 582–583 (invited News & Views article). “Engineered P450 Atom Transfer Radical Cyclases Are Bifunctional Biocatalysts: Reaction Mechanism and Origin of Enantioselectivity“ Yue Fu, Heyu Chen, Wenzhen Fu, Marc Garcia-Borras, Yang Yang* and Peng Liu*, Journal of the American Chemical Society 2022, 144, 13344–13355. “The Many Facets of Green Organometallic Chemistry” Xiongyi Huang* and Yang Yang*, Journal of Organometallic Chemistry 2022, 976, 122398 (invited Foreword). “C–N Bond Forming Radical Rebound Is the Enantioselectivity-Determining Step in P411-Catalyzed Enantioselective C(sp3)–H Amination: A Combined Computational and Experimental Investigation“ Binh Khanh Mai, Natalia M. Neris, Yang Yang* and Peng Liu*, Journal of the American Chemical Society 2022, 144, 11215-11225. “High-throughput discovery of chemical structure-polarity relationships combining automation and machine learning techniques“ Hao Xu, Jinglong Lin, Qianyi Liu, Yuntian Chen, Jianning Zhang, Yang Yang, Michael C. Young, Yan Xu, Dongxiao Zhang* and Fanyang Mo,* Chem 2022, 8, 1-13. “Synthesis of Alkylboronic Esters from Alkyl Iodides” Qianyi Liu, Hao Liang, Shangyong Zhou, Lei Zhang, Jianxin Yang, Yunxing Yin, Yang Yang, Di Qiu and Fanyang Mo* Organic Synthesis 2022, 99, 15-28. “Stereodivergent atom-transfer radical cyclization by engineered cytochromes P450“ Qi Zhou, Michael Chin, Yue Fu, Peng Liu, and Yang Yang*, Science 2021, 374, 1612–1616. “Unveiling the full reaction path of the Suzuki-Miyaura cross-coupling in a single molecule junction” Chen Yang, Lei Zhang, Chenxi Lu, Shuyao Zhou, Xingxing Li, Yanwei Li, Yang Yang, Yu Li, Zhirong Liu, Jinlong Yang, K. N. Houk, Fanyang Mo, Xuefeng Guo, Nature Nanotechnology 2021, 16, 1214–1223. “Navigating the Unnatural Reaction Space: Directed Evolution of Heme Proteins for New-to-Nature Carbene and Nitrene Transfer” Yang Yang and Frances H. Arnold, Accounts of Chemical Research 2021, 54, 1209–1225. “An Enzymatic Platform for the Asymmetric Amination of Primary, Secondary, and Tertiary C(sp3)–H Bonds” Yang Yang, Inha Cho, Xiaotian Qi, Peng Liu* and Frances H. Arnold*, Nature Chemistry 2019, 11, 987–993. “Anodic Oxidation Triggered Divergent 1,2- and 1,4-Group Transfer Reactions of β-Hydroxycarboxylic Acids Enabled by Electrochemical Regulation“ Zhenxing Zhang, Lei Zhang, Xianhao Zhang, Jianxin Yang, Yunxing Yin, Yangye Jiang, Cheng-Chu Zeng, Gang Lu, Yang Yang, Fanyang Mo,* Chemical Science 2020, 11, 12021-12028. “Electro-catalytic oxidative transformation of organic acids for carbon-heteroatom and sulfur-heteroatom bond formation“ Man Li, Junting Hong, Wei Xiao, Yang Yang, Di Qiu, Fanyang Mo,* ChemSusChem 2020, 13, 1661-1687. "Modification of TiO2 Nanoparticles with Organodiboron Molecules Inducing Stable Surface Ti3+ Complex" Yang Cao, Peng Zhou, Yongguang Tu, Zheng Liu, Bo-Wei Dong, Aryan Azad, Dongge Ma, Dong Wang, Xu Zhang, Yang Yang, Shang-Da Jiang, Rui Zhu, Shaojun Guo, Fanyang Mo*, Wanhong Ma, iScience 2019, 20, 195–204. “Zn+ -O- Dual-Spin Surface States Formation by Modification of ZnO Nanoparticles with Diboron Compounds” Yang Cao, Yongguang Tu, Peng Zhou, Jianning Zhang, Yuchen Deng, Biao Kong, Xu Zhang, Shaojun Guo, Rui Zhu, Ding Ma, Yang Yang and Fanyang Mo*, Langmuir 2019, 35, 14173–14179. “Transition-Metal-Free Borylation of Alkyl Halides via a Radical Mechanism” Qianyi Liu, Junting Hong, Beiqi Sun, Guangcan Bai, Feng Li, Guoquan Liu, Yang Yang and Fanyang Mo*, Organic Letters 2019, 21, 6597–6602. “Enantioselective Allylation Using Allene, A Petroleum Cracking Byproduct” Richard Y. Liu†, Yujing Zhou†, Yang Yang and Stephen L. Buchwald*, Journal of the American Chemical Society 2019, 141, 2251–2256. “CuH-Catalyzed Enantioselective Ketone Allylation with 1,3-Dienes: Scope, Mechanism, and Applications.” Chengxi Li, Richard Y. Liu, Luke T. Jesikiewicz, Yang Yang, Peng Liu* and Stephen L. Buchwald*, Journal of the American Chemical Society 2019, 141, 5062–5070. “Mn-Mediated Electrochemical Trifluoromethylation/C(sp2)−H Functionalization Cascade for the Synthesis of Azaheterocycles” Zhenxing Zhang, Lei Zhang, Yang Cao, Feng Li, Guangchan Bai, Guoquan Liu, Yang Yang and Fanyang Mo*, Organic Letters 2019, 21, 762–766.

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