Engineering Heme Enzymes to Navigate New-to-Nature Reaction Space

Title:

Engineering Heme Enzymes to Navigate New-to-Nature Reaction Space

Schedule:

Date: 21^st March, 2024 (Thursday)

Time: 5:30 - 6:30 pm (HKT)

Venue: Lecture Theatre P2, Chong Yuet Ming Physics Building

Speaker:

Dr. Runze MAO

Department of Chemistry and Chemistry Engineering

California Institute of Technology

Biography:

Dr. Runze Mao is currently a postdoctoral researcher in the group of Prof. Frances Arnold (2018 Nobel Prize laureate in Chemistry for pioneering the use of directed evolution to engineer enzymes) at the California Institute of Technology (Caltech). Dr. Mao began his scientific career at Peking University under the supervision of Prof. Xin-Shan Ye (叶新山), mainly focusing on developing noncanonical glycosylation reactions. There he developed two photo-induced glycosylation methods that were later applied to automated glycan assembly by the same lab. After obtaining his master's degree with honors in 2016, Dr. Mao moved to the other end of the Eurasian continent and joined the group of Professor Xile Hu (胡喜乐) at the Swiss Federal Institute of Technology in Lausanne (EPFL), where he focused on 3d-metal-catalyzed transformations. Dr. Mao innovated several catalytic methodologies by synergizing traditional catalytic approaches. This enabled the rapid construction of compounds rich in sp3-hybridized carbon centers, transcending the "flatland" of molecules and unlocking new chemical space essential for medicinal chemistry applications. In September 2020, he received his PhD degree in chemistry with honors and thesis awards. Due to global travel restrictions during the pandemic, Dr. Mao enjoyed a brief 3-month postdoctoral stint in the same lab. In January 2021, he made a bold career move by crossing the Atlantic Ocean to join Prof. Frances Arnold's group at Caltech. This decision marked a significant shift from his previous focus on chemistry and chemical catalysis to biochemistry and biocatalysis. Remarkably, it proved to be a perfect choice, as Dr. Mao discovered a profound passion, immersing himself in this new field with great enthusiasm. At Caltech, Dr. Mao mastered the art of leveraging directed evolution to impart new talents to “old” enzymes. He significantly expanded the catalytic repertoire of these enzymes, addressing pressing challenges at the interface of biocatalysis and synthetic chemistry. His research has been fruitful, with 15 first-author and 7 co-author publications. He has received many awards, including the Clarendon and Marie Curie Scholarships, Reaxys Global PhD Prize finalist, PhD Thesis Award, and the Chinese Government Award for Outstanding Self-Financed Students Abroad.

Abstract:

DNA-programmable chemical synthesis using enzymes holds great potential to advance conventional synthetic processes, especially in sustainability, efficiency, and selectivity. Despite its promise, enzyme catalysis is currently hampered by a limited catalytic repertoire. To address this, we have leveraged directed evolution to engineer heme enzymes that push the boundaries of nature’s synthetic capabilities. These research endeavors have unlocked previously unknown chemical space of enzyme catalysis and overcome synthetic challenges where existing biological and synthetic methods falter. Moreover, combined experiments and computational studies, including DFT calculations and MD simulations, have deepened our understanding of these heme enzymes' novel functions.

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