A team of 23 researchers from the Tang, Houk and Garg labs receive the RSC’s 2021 Horizon Prize: Bioorganic Chemistry Award for their discovery of a new class of enzymes.
The collaboration between the Tang, Houk and Garg labs at UCLA, led by a team of postdoctoral scholars and graduate students, discovered and characterized a family of natural enzymes called the pericyclases. According to the RSC announcement, the inaugural 2021 Horizon Prizes “recognise the most exciting, contemporary science, the prizes are awarded to teams or collaborations that are opening up new directions and possibilities in their field.”
Team Pericyclases (17 of the 23 team members)
The award is unique in that recognizes all the team members behind the discovery. The “Team Pericyclases” members are (in alphabetical order):
Sarah Anthon
y (Garg PhD student),
Dr. Joyann Barber
(Pfizer, PhD with Garg),
Yujuan Cai
(PhD student, Shanghai Institute of Organic Chemistry),
Dr. Shugeng Cao
(Assoc. Professor, University of Hawaii, Hilo),
Jason Char
i (Garg PhD student),
Dr. Mengbin Chen
(Tang postdoc),
Dr. Marc Garcia-Borràs
(Girona, Spain, former Houk postdoc), Professor Neil Garg,
Dr. Yang Hai
(Asst. Professor, UC Santa Barbara, former Tang postdoc), Professor Ken Houk,
Cooper Jamieson
(Houk/Tang PhD student),
Dr. Thomas Kakule
(Ginkgo, former Tang postdoc),
Daiki Kanayama
(former Tang undergrad),
Dr. Fang Liu
(Professor, Nanjing Agricultural University, PhD with Houk, former postdoc with Houk and Tang),
Dr. Masao Ohashi
(postdoc, Tang group),
Dr. Elias Picazo
(postdoc, Harvard, PhD with Garg),
Dr. Michio Sato
(Asst. Professor, University of Shizuoka, former Tang postdoc),
Dr. Dan Tan
(former visiting scientist with Tang), Professor Yi Tang,
Dr. Man-cheng Tang
(Assoc. Professor, Shanghai Jiao Tong University, former Tang postdoc),
Dr. Kenji Watanabe
(Collaborator, University of Shizuoka),
Dr. Zhongyue Yang
(Professor, Vanderbilt University, PhD with Houk),
Dr. Jiahai Zhou
(Professor, Shanghai Institute of Organic Chemistry).
“By combining enzyme discovery, mutational studies, X-ray crystallography, quantum mechanics, molecular dynamics, and synthetic chemistry, the 23 members of our team, located in the US, China, Japan, and Spain, have revealed previously unknown secrets of nature,” said team leaders Professors Yi Tang and Ken Houk.
Pericyclases catalyse structure and pericyclases in the lab
Enzymes are proteins found naturally in cells, facilitating and speeding up chemical reactions within the cell. Pericyclases catalyse a special class of organic reactions called pericyclic reactions – where the reactants are converted by a cyclic transition state into products without formation of intermediate structures. These reactions are commonplace in laboratory synthesis of small molecules (i.e. commodity chemicals or pharmaceuticals) and are often considered ‘abiological’ or ‘invented’ by synthetic chemists.
The team’s discovery means that we now know that nature uses this chemistry, revealing an entire “toolbox” of enzymes that catalyse reactions previously not known. This fundamentally shifts our knowledge on how nature constructs complex molecules that are essential for life, opening up new opportunities in chemical synthesis.
Using an interdisciplinary approach combining genetics, biochemistry, structural biology and computational science, the team have studied these pericyclases to understand how the enzymes evolved and the mechanisms behind the catalysis.
This fundamental understanding means the team can modify the enzymes to alter and therefore control what reaction is catalysed. This increases the potential of these enzymes in synthetic chemistry even further, and provides proof-of-concept that enzymes can be artificially modified in the lab for new applications.
UCLA’s “Team Pericyclases” leaders – Professor Neil Garg, Professor Ken Houk, graduate student Cooper Jamieson, postdoc Dr. Masao Ohashi, and Professor Yi Tang.
The RSC Horizon award announcement website includes inspiring quotes from team leaders Professors Yi Tang and Ken Houk and postdoctoral scholar Dr. Masao Ohashi and graduate student Cooper Jamieson.
Read more about the research:
“An Enzymatic Alder-ene Reaction” Nature. 2020, 586, 64-69. Ohashi, M., Jamieson, C. S., Cai, Y., Tan, D., Kanayama, D., Tang, M., Anthony, S. M., Chair, J. V., Barber, J. S., Picazo, E., Kakule, T. B., Cao, S., Garg, N. K., Zhou, J., Houk, K. N., Tang, Y. Read a news article about this paper here.
“Structural Basis for Stereoselective Dehydration and Hydrogen-Bonding Catalysis by the SAM-Dependent Pericyclase LepI” Nature Chemistry, 2019, 11, 812–820. Cai, Y., Hai, Y., Ohashi, M., Jamieson, C. S., Garcia-Borras, M., Houk, K. N., Zhou, J., Tang, Y.
“SAM-Dependent Enzyme-Catalysed Pericyclic Reactions in Natural Product Biosynthesis” Nature, 2017, 549, 502–506. Ohashi, M., Liu, F., Hai, Y., Chen, M., Tang, M-C., Yang, Z., Sato, M., Watanabe, K., Houk, K. N., Tang, Y.,
Penny Jennings, UCLA Department of Chemistry & Biochemistry, penny@chem.ucla.edu.
