Publications — Yang Lab at UCSB

At UCSB

2024

61. “Artificial Boron Enzymes“ Xiao-Wang Chen, Zhiyu Bo, and Yang Yang*, Nature Chemical Biology 2024, 20, 1106–1107 (invited News & Views article).

60. “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. († denotes equally contributing authors)

59. “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.

58. “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.

**About the Cover:** Pyridoxal 5´-phosphate (PLP) enzymes are essential biosynthetic machinery underlying amino acid metabolism. Now, through visible light induced free radical initiation, PLP-dependent threonine aldolases are repurposed to catalyze asymmetric intermolecular free radical coupling reactions for amino acid synthesis.

Highlighted by Hisashi Yamamoto, Tomohiro Hattori in Synfacts 2024, 20, 1108: “Aldolase-Catalyzed Enantioselective Amino Acid Synthesis from Glycine”

57. “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*, Proceedings of the 41st International Conference on Machine Learning (ICML), 2024, PMLR 235:46259-46279.

Preprint from Arxiv is available here.

56. “Unnatural Thiamine Radical Enzymes for Photobiocatalytic Asymmetric Alkylation of Benzaldehydes and α-Ketoacids“ Xin Liu, Sheng Xu, Heyu Chen and Yang Yang*, ACS Catalysis 2024, 14, 9144–9150.

Preprint from ChemRxiv is available here.

55. “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.

Featured in UCSB’s The Current: Shining light on new chemical reactions
Highlighted by Hisashi Yamamoto and Abhijit Paul in Synfacts 2024, 20 (08), 0882: Amino Acid Synthesis via Photobiocatalytic Asymmetric C(sp3)–C(sp3) Oxidative Cross-Coupling

54. ”A metalloenzyme platform for catalytic asymmetric radical dearomatization“ Wenzhen Fu, Yue Fu, Yunlong Zhao, Huanan Wang, Peng Liu* and Yang Yang*, Nature Chemistry 2024, published online, DOI: 0.1038/s41557-024-01608-8.

Highlighted by Benjamin List and Lennart J. Brücher in Synfacts 2024, 20, 1193, “Enzymatic Asymmetric Radical Dearomatization of Electron-Rich Arenes Towards Chiral Spirocycles”

53. “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, 3, 967–975.

Preprint from ChemRxiv available here.

See a highlight from Kyle Biegaziewicz: “A radical development for enzymatic fluorination“ Nature Synthesis 2024, DOI: s44160-024-00540-6.

52. ”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, 16, 1339–1347.

Featured in Chemistry World: Light-driven enzyme engineered and repurposed to catalyse unnatural reaction
Highlighted by Benjamin List and Margareta M. Poje in Synfacts 2024, 20 (07), 0746: Stereodivergent Radical Cyclizations Enabled by Directed Evolution of Fatty Acid Photodecarboxylases

2023

51. “Young Career Focus: Assistant Professor Yang Yang (University of California Santa Barbara, USA)“ Synform 2023, 12, A196–A199.

50. “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.

49. “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.

48. “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).

47. “Practical Biocatalytic Synthesis of Aromatic Nitriles“ Zhiyu Bo and Yang Yang*, Chem Catalysis 2023, 3, 100615 (invited Preview).

46. “Enzymes on Steroids“ Liupeng Zhao, Zhiyu Bo and Yang Yang*, Nature Synthesis 2023, 2, 699–700 (invited News & Views).

45. “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.

Featured in C&E News: Enzyme and photocatalyst team up to make nonnatural amino acids
Featured in the Current: A new synergistic method can create non-canonical amino acids by merging synthetic photochemistry with biocatalysis
Featured in ScienceDaily: New chemical process makes it easier to craft amino acids that don't exist in nature
Highlighted by Benjamin List and Margareta M. Poje in Synfacts 2023, 19(11), 1142: Stereoselective Synthesis of Noncanonical Amino Acids Enabled by Photoredox-Pyridoxal Radical Biocatalysis
Highlighted by Yuxuan Ye in Chem Catalysis 2023, 3, 100753: Synergistic photoredox-pyridoxal radical biocatalysis enables synthesis of noncanonical amino acids

44. “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.

43. “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.

Stereocontrolled free-radical-mediated reactions are notoriously challenging. Now, Peng Liu, Yang Yang and colleagues report the directed evolution of cytochrome P450 enzymes for the asymmetric radical cyclization of α-haloesters to arenes. Complementary P450 radical cyclases are obtained allowing access to both enantiomeric products.

Featured on the cover of Nature Catalysis (July 2023 issue).
Highlighted by UCSB’s The Current: Sonia Hernandez, “A ‘toolbox of biocatalysts’ improves control over free radicals“
Highlighted by Paul Richardson in Synfacts 2024, 20, 0012, “Enzyme-Catalyzed Synthesis of Chiral 3,3-Disubstituted Oxindoles“

2022

42. “Undirected Biocatalytic Amination of Unactivated C(sp3)-H Bonds” Wenzhen Fu and Yang Yang*, Chem Catalysis 2022, 2, 3287-3289 (invited Preview).

41. “Photoenzymes for Radical C-C Coupling“ Rui Guo, Heyu Chen and Yang Yang*, Nature Catalysis 2022, 5, 582–583 (invited News & Views article).

40. “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.

39. “The Many Facets of Green Organometallic Chemistry” Xiongyi Huang* and Yang Yang*, Journal of Organometallic Chemistry 2022, 976, 122398 (invited Foreword).

38. “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.

• Selected as the cover story of the Journal of the American Chemical Society

**About the Cover:** A combined computational and experimental study reveals that, contrary to previously hypothesized enantioinduction mechanisms, the radical rebound step is enantioselectivity-determining under the Curtin–Hammett conditions, whereas the preceding HAT step is only moderately stereoselective. This study highlights an unusual enantioinduction mechanism in metalloenzyme-catalyzed asymmetric transformations involving radical intermediates. Cover art by Binh Khanh Mai.

37. “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.

• Selected as the cover art of Chem.

36. “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.

2021

35. “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.

For highlights, see:

“Teaching natural enzymes new radical tricks“ Yang Zhang and Pawel Dydio, Science 2021, 374, 1558–1559.
“Engineered Metalloenzymes Permit Stereodivergent Radical Cyclization of Alkyl Bromides“ Benjamin List and Sebastian Brunen, Synfacts 2022, 18, 0308.
“Evolved enzymes carry out new-to-nature radical chemistry” Chemistry World, 2022.
“Versatility and Selectivity“ UCSB The Current, 2022.

34. “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.

33. “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.

• Selected as the cover story of Accounts of Chemical Research in the March issue.

The catalytic repertoire of heme proteins covers an astonishing range of reactions in nature. Now, enabled by directed evolution, cytochromes P450 and other heme proteins have been repurposed to catalyze a large and growing set of carbene and nitren… — **About the Cover:** The catalytic repertoire of heme proteins covers an astonishing range of reactions in nature. Now, enabled by directed evolution, cytochromes P450 and other heme proteins have been repurposed to catalyze a large and growing set of carbene and nitrene transfer reactions previously unknown in biology. Cover art by Lei Chen. See article by Yang Yang and Frances H. Arnold (DOI: 10.1021/acs.accounts.0c00591).

Prior to UCSB

32. “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.

31. “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.

30. “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.

29. "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.

28. “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.

27. “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.

26. “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.

25. “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.

24. “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.

23. “A General Electrochemical Strategy for the Sandmeyer Reaction” Qianyi Liu, Beiqi Sun, Zheng Liu, Yi Kao, Bo-Wei Dong, Shang-Da Jiang, Feng Li, Guoquan Liu, Yang Yang and Fanyang Mo*, Chemical Science 2018, 9, 8731–8737.

22. “A Regio- and Enantioselective CuH-Catalyzed Ketone Allylation with Terminal Allenes” Erica Y. Tsai, Richard Y. Liu, Yang Yang and Stephen L. Buchwald*, Journal of the American Chemical Society 2018, 140, 2007–2011.

21. “Palladium-Catalyzed Cross-Coupling of Nitroarenes." Yang Yang*, Angewandte Chemie International Edition 2017, 56, 15802–15804.

20. “Ligand-Substrate Dispersion Facilitates the Copper-Catalyzed Hydroamination of Unactivated Olefins" Gang Lu, Richard Y. Liu, Yang Yang, Cheng Fang, Daniel S. Lambrecht*, Stephen L. Buchwald* and Peng Liu*, Journal of the American Chemical Society 2017, 139, 16548–16555.

19. “Copper-Catalyzed Enantioselective Addition of Styrene-Derived Nucleophiles to Imines Enabled by Ligand-Controlled Chemoselective Hydrocupration" Yang Yang, Ian B. Perry and Stephen L. Buchwald*, Journal of the American Chemical Society 2016, 138, 9787–9790.

• Featured in Synfacts 2016, 12, 1157.

18. “CuH-Catalyzed Regiodivergent and Stereoselective Allylation of Imines from Terminal Allenes" Richard Y. Liu, Yang Yang and Stephen L. Buchwald*,Angewandte Chemie International Edition 2016, 55, 14077–14080.

• Featured in Synfacts 2016, 12, 1258.

17. “Copper-Catalyzed Asymmetric Addition of Olefin-Derived Nucleophiles to Ketones" Yang Yang, Ian B. Perry, Gang Lu, Peng Liu* and Stephen L. Buchwald*, Science 2016, 353, 144–150.

• Highlighted by Chemistry & Engineering News 2016, 94, 8.
• Highlighted by Prof. Martin Oestreich in Angewandte Chemie International Edition 2016, 55, 12148.
• Featured in Synfacts 2016, 12, 923.

16. “Regio- and Stereospecific 1,3-Allyl Group Transfer Triggered by a Copper-Catalyzed Borylation/ortho-Cyanation Cascade" Yang Yang*, Angewandte Chemie International Edition 2016, 55, 345–349.

• Featured in Synfacts 2016, 12, 83.

15. “A Fluorinated Ligand Enables Room Temperature and Regioselective Pd-Catalyzed Fluorination of Aryl Triflates and Bromides” Aaron C. Sather, Hong Geun Lee, Valentina De La Rosa, Yang Yang, Peter Müller and Stephen L. Buchwald*, Journal of the American Chemical Society 2015, 137, 13433–13438.

14. “In-Depth Assessment of the Pd-Catalyzed Fluorination of 5-Membered Heteroaryl Bromides” Philip J. Milner, Yang Yang and Stephen L. Buchwald*, Organometallics 2015, 34, 4775–4780.

13. “Catalytic Asymmetric Hydroamination of Unactivated Internal Olefins to Aliphatic Amines” Yang Yang†, Shi-Liang Shi†, Dawen Niu, Peng Liu and Stephen L. Buchwald*, Science 2015, 349, 62–66.

• Highlighted by Chemistry & Engineering News 2015, 93, 9.
• Highlighted by Chemistry World 2015.
• Featured in Organic Process Research & Development 2015, 19, 1703–1710 as an item of interest to process R&D chemists and engineers.
• Featured in Synfacts 2015, 11, 946.

12. Yang Yang and Peng Liu*, “Mechanism and Origins of Selectivities in the Copper-Catalyzed Dearomatization Induced C–H Cyanation of Vinylarenes” ACS Catalysis 2015, 5, 2944–2951.

• Selected by Profs. Paul J. Chirik and T. Brent Gunnoe in the joint virtual issue between Organometallics and ACS Catalysis on first-row transition-metal complexes: ACS Catal. 2015, 5, 5584−5585.

11. “Highly Selective Palladium-Catalyzed Cross-Coupling of Secondary Alkylzinc Reagents with Heteroaryl Halides” Yang Yang, Katrin Niedermann, Chong Han and Stephen L. Buchwald*, Organic Letters 2014, 16, 4638–4641.

10. “N-Cyano-4-methyl-N-phenyl-benzenesulfonamide” Yang Yang and Jianbo Wang*, Encyclopedia of Reagents for Organic Synthesis 2014, DOI: 10.1002/047084289X.rn01643 (Review).

9. “Copper-Catalyzed Regioselective ortho C–H Cyanation of Vinylarenes” Yang Yang and Stephen L. Buchwald*, Angewandte Chemie International Edition 2014, 53, 8677–8681.

8. “Palladium-CatalyzedCompletely Linear-Selective Negishi Cross-Coupling of Allylzinc Halides with Aryl and Vinyl Electrophiles” Yang Yang, Thomas J. L. Mustard, Paul Ha-Yeon Cheong* and Stephen L. Buchwald*, Angewandte Chemie International Edition 2013, 52, 14098–14102.

• Selected by the editor of Angewandte Chemie as a hot paper.
• Featured in Synfacts 2014, 10, 297.

7. “Ligand Controlled Palladium-Catalyzed Regiodivergent Suzuki–Miyaura Cross-Coupling of Allylboronates and Aryl Halides.” Yang Yang and Stephen L. Buchwald*, Journal of the American Chemical Society 2013, 135, 10642–10645.

6. “Mild and General Conditions for Negishi Cross-Coupling Enabled by the Use of Palladacycle Precatalysts” Yang Yang, Nathan J. Oldenhuis, and Stephen L. Buchwald*, Angewandte Chemie International Edition 2013, 52, 615–619.

• Featured in Organic Process Research & Development 2013, 17, 320–329 as an item of interest to process R&D chemists and engineers.

5. “Pd-Catalyzed Three-Component Reaction of Allenes, Aryl Iodides and Diazo Compounds: New Approach to 1,3-Dienes” Qing Xiao, Binglong Wang, Leiming Tian, Yang Yang, Jian Ma, Yan Zhang, Shufeng Chen* and Jianbo Wang*, Angewandte Chemie International Edition 2013, 52, 9305–9308.

4. “Auto-Tandem Catalysis: Synthesis of Acridines by Pd-Catalyzed C=C Double Bond Formation and C(sp2)-N Cross-Coupling” Zhongxing Huang, Yang Yang, Qing Xiao, Yan Zhang and Jianbo Wang*, European Journal of Organic Chemistry 2012, 33, 6586–6593.

3. “Lewis Acid-Catalyzed Direct Cyanation of Indoles and Pyrroles with N-Cyano-N-phenytoluenesulfonamide (NCTS)” Yang Yang and Jianbo Wang*, Organic Letters 2011, 13, 5608–5611.

2. “Nickel-Catalyzed Amination of Aryl Sulfamates” Stephen D. Ramgren, Amanda L. Silberstein, Yang Yang and Neil K. Garg*, Angewandte Chemie International Edition 2011, 50, 2171–2173.

• Featured in Synfacts 2011, 5, 471.

1. “Pd-Catalyzed C=C Double Bond Formation by Coupling of N -Tosylhydrazones with Benzyl Halides” Qing Xiao, Jian Ma, Yang Yang, Yan Zhang and Jianbo Wang*, Organic Letters 2009, 11, 4732–4735.

• Featured in Synfacts 2010, 1, 91.