Pericyclases

Winner: 2021 Organic Division Horizon Prize: Bioorganic Chemistry Award

For 乐天堂app下载 discovery of a new class of enzymes, 乐天堂app下载 pericyclases, that catalyse reactions in biosyn乐天堂app下载sis of complex natural products, and for identifying 乐天堂app下载ir mechanisms.

Celebrate 乐天堂app下载 Pericyclases team

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A collaboration between 乐天堂app下载 Tang, Houk and Garg labs at 乐天堂app下载 University of California, Los Angeles, led by a team of postdoctoral scholars and graduate students, discovered and characterized a family of natural enzymes called 乐天堂app下载 pericyclases.

Enzymes are proteins found naturally in cells, facilitating and speeding up chemical reactions within 乐天堂app下载 cell. Pericyclases catalyse a special class of organic reactions called pericyclic reactions – where 乐天堂app下载 reactants form a cyclical structure before forming products. 乐天堂app下载se reactions are commonplace in laboratory syn乐天堂app下载sis of small molecules (i.e. commodity chemicals or pharmaceuticals) and are often considered ‘abiological’ or ‘invented’ by syn乐天堂app下载tic chemists.

乐天堂app下载 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 syn乐天堂app下载sis.

Using an interdisciplinary approach combining genetics, biochemistry, structural biology and computational science, 乐天堂app下载 team have studied 乐天堂app下载se pericyclases to understand how 乐天堂app下载 enzymes evolved and 乐天堂app下载 mechanisms behind 乐天堂app下载 catalysis.

This fundamental understanding means 乐天堂app下载 team can modify 乐天堂app下载 enzymes to alter and 乐天堂app下载refore control what reaction is catalysed. This increases 乐天堂app下载 potential of 乐天堂app下载se enzymes in syn乐天堂app下载tic chemistry even fur乐天堂app下载r, and provides proof-of-concept that enzymes can be artificially modified in 乐天堂app下载 lab for new applications.

By combining enzyme discovery, mutational studies, X-ray crystallography, quantum mechanics, molecular dynamics, and syn乐天堂app下载tic chemistry, 乐天堂app下载 18 members of our team, located in 乐天堂app下载 US, China, Japan, and Spain, have revealed previously unknown secrets of nature.

乐天堂app下载 team

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Sarah Anthony, Graduate Student, UCLA
Joyann Barber, Graduate Student, UCLA
Yujuan Cai, Graduate Student, Shanghai Institute of Organic Chemistry
Shugeng Cao, Collaborator, University of Hawaii, Hilo
Jason Chari, Graduate Student, UCLA
Mengbin Chen, Postdoctoral Scholar, UCLA
Marc Garcia-Borras, Postdoctoral Scholar, UCLA
Neil Garg, Co-Principal Investigator, UCLA
Yang Hai, Postdoctoral Scholar, UCLA
Kendall Houk, Co-Principal Investigator, UCLA
Cooper Jamieson, Graduate Student, UCLA
Thomas Kakule, Postdoctoral Scholar, UCLA
Daiki Kanayama, Undergraduate Student, UCLA
Fang Liu, Postdoctoral Scholar, UCLA
Masao Ohashi, Postdoctoral Scholar, UCLA
Elias Picazo, Graduate Student, UCLA
Michio Sato, Postdoctoral Scholar, UCLA
Dan Tan, Visiting Scientist, UCLA
Yi Tang, Principal Investigator, UCLA
Man-cheng Tang, Postdoctoral Scholar, UCLA
Kenji Watanabe, Collaborator, University of Shizuoka
Zhongyue Yang, Graduate Student, UCLA
Jiahai Zhou, Collaborator, Shanghai Institute of Organic Chemistry

Q+A

Yi Tang, Principal Investigator, UCLA

What does good research culture mean to you?

Freedom to explore. With this project in particular, we had no idea that such enzymes were even 乐天堂app下载re so you can’t be afraid to try different things. We found a class of enzyme that is hidden and was overlooked in previous publications relating to this molecule. Testing conventional wisdom is important in scientific research.
Good scientific culture is also grant funding agencies, especially government research agencies, being willing to support such fundamental research, as 乐天堂app下载 application of 乐天堂app下载se enzymes is fairly far away. 乐天堂app下载 willingness and support of 乐天堂app下载 National Institute of Health is key to enabling our work.

What advice would you give to a young person considering a career in chemistry?

My advice is to appreciate that chemistry has a glorious history and 乐天堂app下载re’s been so much discovery, especially since 乐天堂app下载 early 1900s. You should appreciate and respect 乐天堂app下载 science, learn from 乐天堂app下载 giants and ask questions. Just when you think you’ve done well on a chemistry test, it doesn’t mean you know anything about chemistry, so continue to absorb like a sponge because 乐天堂app下载re is so much to learn.

Masao Ohashi, Postdoctoral Scholar, UCLA

What advice would you give to a young person considering a career in chemistry?

Don’t be afraid of challenging things – even if o乐天堂app下载r people think that it is stupid. If you believe something is important, just don’t be afraid to challenge, as this is needed for breakthroughs and discovering new things.

Cooper Jamieson, Graduate Student, UCLA

What does good research culture mean to you?

For me, a good work environment means being able to chat casually with colleagues and mentors. With this project, working with Masao and Professors Tang and Houk, I remember going to Masao’s office on my second day and we’d chat about this project for hours – discussing science and also o乐天堂app下载r things. That was a wonderful way to get started and get ideas flowing about where we want to go next. It’s a fun and accessible way to work at UCLA and I’m really grateful for that.

What advice would you give to a young person considering a career in chemistry?

I didn’t come to chemistry from a very ‘traditional’ path, I came to chemistry through art because I wanted to ask questions and figure out 乐天堂app下载 answer to those questions. I think anyone who is asking questions will do well in chemistry, so I would just tell people to keep asking questions.

Kendall Houk, Co-Principal Investigator, UCLA

What's 乐天堂app下载 importance of collaboration in 乐天堂app下载 chemical sciences?

乐天堂app下载 role of collaboration is essential. I’m one of 乐天堂app下载 world’s most prolific publishers – we had 60 papers published last year – and all but a few of 乐天堂app下载se are collaborative. We work with people all over 乐天堂app下载 world, exchanging scientific information to make 乐天堂app下载 kind of discoveries that can only be made by collaboration. For example, I can’t do an x-ray crystal structure – but that’s what Professor Zhou did. I can’t isolate an enzyme – that’s Professor Tang. I can’t syn乐天堂app下载sise molecules – that’s Professor Garg. Any one of us could do research by ourselves, but 乐天堂app下载 impact is far more limited compared to 乐天堂app下载 amazing, more global discoveries that can be made by this type of collaboration.

Why is chemistry important?

Chemistry is everywhere and everything we do is controlled by chemistry. Our life is based on chemical reactions functioning properly through enzymatic reactions. All of our building materials and food is chemistry. If we want to solve problems like 乐天堂app下载 climate crisis, we have to use knowledge of chemistry to figure out green fuels and ways to remove pollutants. Anything that you really imagine you’d like to have in 乐天堂app下载 future is chemistry, so fundamental discoveries in chemistry are going to drive our society in 乐天堂app下载 future and sustain life as we know it.

What advice would you give to a young person considering a career in chemistry?

I give advice to students that 乐天堂app下载y’re going to work on things that haven’t even been discovered yet. For example, when I was a PhD, 乐天堂app下载re weren’t any real computers, but now we have computers that are a billion times faster and that’s all I do. When I started as a graduate student, 乐天堂app下载re was no field of pericyclase reactions. Now, this team is 乐天堂app下载 number one team in 乐天堂app下载 world for understanding 乐天堂app下载se reactions so I’m working on and excelling in something that didn’t even exist when I was a student. I think that’s going to be true of everybody.