Enzyme Platform Development for Sustainable Production of Bioactive Aminoketone Derivatives

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About This Project

Unlike traditional chemical industry, enzymatic syntheses align with green chemistry principles, affording unmatched selectivity and fostering eco-friendly chemical conversions. In this proposal, we aim to engineer a hemoprotein for facile construction of pivotal C–N bonds. This innovative enzymatic platform seeks to convert feedstock chemicals into value-added compounds, such as aminoketones, ushering synthetic chemistry into a sustainable, efficient, and environmentally conscious age.

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What is the context of this research?

The chemical industry has a huge impact on society: this sector produces a vast array of products in every aspect of our daily lives. These myriad contributions come with considerable downsides, including the heavy environmental footprint of its production processes, which generate substantial amounts of greenhouse gases and toxic chemical wastes. One path toward more sustainable chemical synthesis is the increased utilization of enzymes. Enzymes exhibit extraordinary abilities in constructing molecules with high activity, selectivity, and sustainability—using biocatalysis in chemical production can greatly reduce toxic waste and the carbon footprint of the chemical industry. We are expanding the repertoire of biocatalysis with reactions that are useful.

What is the significance of this project?

Traditional synthesis of some bioactive molecules, which constitute a multi-billion-dollar market in the pharmaceutical industry, often requires energy-intensive, multi-step chemical processes that generate significant waste, like noble metals and organic solvents. Developing an enzymatic approach to construct those molecules not only aligns with the tenets of green chemistry but also delivers unparalleled selectivity, a cornerstone for efficient drug development. We aim to engineer a hemoprotein to facilitate the precise and efficient incorporation of functional groups into diverse molecular structures. This new-to-nature enzymatic platform will leverage the ability of enzymes to transform simple feedstock chemicals into valuable pharmaceutical compounds bearing an array of motifs.

What are the goals of the project?

The primary objective is to engineer a thermostable hemoprotein that facilitates the enzymatic construction of bioactive molecules through an efficient biocatalytic transformation. Leveraging the power of directed evolution, we intend to introduce and select for mutations that enhance the desired activity, which is present as a ‘promiscuous’ activity of various hemoproteins. Building on this, we can extend this methodology to synthesize other molecular moieties by tuning the substrate structures. The second objective is to show gram-scale enzymatic synthesis which is critical for industrial application. Ultimately, our vision is to establish an efficient and eco-friendly enzymatic platform capable of forging valuable molecules from low-cost feedstock chemicals.


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The total budget amount of $125,000 will support the costs for materials and supplies and team member salaries that is necessary to accomplish our goals and objectives outlined in this proposal.

Project Timeline

12/1/2023-1/31/2024 - Literature review and initial project setup: find target molecules and screen for variants with desired functions

2/1/2024-3/31/2024 - Experimental protocol development and data collection

4/1/2024-12/31/2024 - Directed evolution to improve enzyme functions

1/1/2025-4/30/2025 – Exploring the substrate compatibility with optimal variants and conducting mechanistic studies

8/1/2024-11/30/2025 - Based on acquired data, utilizing machine learning to aid protein engineering

Jan 31, 2024

Identify initial variants with desired functions

Aug 31, 2024

Train machine learning model based on acquired data

Dec 31, 2024

Identify optimal variants for desired functions

Apr 30, 2025

Finish the exploration of substrate compatibility

Nov 30, 2025

Set up the complete enzymatic platform

Meet the Team

Ziyang Qin
Ziyang Qin
Graduate Student


California Institute of Technology
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Frances H. Arnold
Frances H. Arnold
Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry


California Institute of Technology
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Team Bio

Arnold Lab - Website

Arnold lab develops evolutionary protein design methods to elucidate principles of biological design and generate novel and useful enzymes and organisms.

Ziyang Qin

Ziyang Qin is a Ph.D. candidate in Chemical Biology at the California Institute of Technology, under the guidance of Prof. Frances Arnold. He earned a B.S. in Chemistry from University of Science and Technology of China and also conducted two research internships at The Scripps Research Institute and the Massachusetts Institute of Technology, respectively. His expertise includes protein engineering, biocatalysis, and synthetic chemistry. Outside the lab, Ziyang enjoys traveling, hiking, immersing himself in art museums, hunting for delicious food.

Frances H. Arnold

Frances Arnold is the Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry at the California Institute of Technology. Arnold pioneered directed enzyme evolution, for which she was awarded the Nobel Prize in Chemistry in 2018; she has used directed protein evolution for applications in alternative energy, chemicals, and medicine. Arnold was recently appointed to co-chair the President’s Council of Advisors on Science and Technology. Among other awards, Arnold has received the Charles Stark Draper Prize of the US National Academy of Engineering (2011), the US National Medal of Technology and Innovation (2011), and the Millennium Technology Prize (2016). She has been elected to the US National Academies of Science, Medicine, and Engineering and was appointed to the Pontifical Academy of Sciences in 2019. Arnold co-founded three companies in sustainable chemistry and renewable energy (Gevo, Provivi, Aralez Bio) and serves on several public and private company boards. She earned a B.S. in Mechanical and Aerospace Engineering from Princeton University and a Ph.D. in Chemical Engineering from the University of California, Berkeley.

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