Design and Evolution of Photoenzymes for Triplet Energy Transfer Catalysis
Lead Research Organisation:
University of Manchester
Department Name: Chemistry
Abstract
The ability to program new modes of catalysis into enzymes would have profound impacts across chemistry
and biotechnology, delivering sustainable biocatalytic processes to address societal needs. Genetic code
expansion technology opens up exciting new opportunities in biocatalyst design and engineering, by
allowing site-selective introduction of new functional elements into proteins as non-canonical amino acid
side chains. In TRIPase, I will exploit an expanded genetic code to develop efficient, selective and
programmable photoenzymes that operate via triplet energy transfer processes, a versatile mode of reactivity
in organic synthesis that is currently not accessible to biocatalysis. These photoenzymes will contain
functional elements needed to harness light energy and promote valuable chemical reactions including [2+2]
cycloadditions, electrocyclizations, rearrangements and deracemizations. My approach will employ
engineered translation components to introduce organic photosensitizers into protein active sites. Protein
cavities offer attractive and versatile chiral environments for mediating enantioselective photochemistry,
where substrates and key catalytic elements can be accurately positioned within a single pocket. Since the
photosensitizers are genetically encoded, active photoenzymes can be optimized via directed evolution to
enhance catalytic efficiency and quantum yields, or to impart new functions that are challenging to achieve
with small molecule photocatalysts. Structural and biochemical analysis of engineered photoenzymes will
shed light on the active site features and mechanistic strategies responsible for enhanced photocatalysis to
guide future biocatalyst design. Overall, the platform technology developed in TRIPase will open the door to
a wealth of new excited-state chemistry in proteins and in doing so will underpin the development of a new
generation of evolvable photocatalysts with efficiencies and specificities akin to natural enzymes.
and biotechnology, delivering sustainable biocatalytic processes to address societal needs. Genetic code
expansion technology opens up exciting new opportunities in biocatalyst design and engineering, by
allowing site-selective introduction of new functional elements into proteins as non-canonical amino acid
side chains. In TRIPase, I will exploit an expanded genetic code to develop efficient, selective and
programmable photoenzymes that operate via triplet energy transfer processes, a versatile mode of reactivity
in organic synthesis that is currently not accessible to biocatalysis. These photoenzymes will contain
functional elements needed to harness light energy and promote valuable chemical reactions including [2+2]
cycloadditions, electrocyclizations, rearrangements and deracemizations. My approach will employ
engineered translation components to introduce organic photosensitizers into protein active sites. Protein
cavities offer attractive and versatile chiral environments for mediating enantioselective photochemistry,
where substrates and key catalytic elements can be accurately positioned within a single pocket. Since the
photosensitizers are genetically encoded, active photoenzymes can be optimized via directed evolution to
enhance catalytic efficiency and quantum yields, or to impart new functions that are challenging to achieve
with small molecule photocatalysts. Structural and biochemical analysis of engineered photoenzymes will
shed light on the active site features and mechanistic strategies responsible for enhanced photocatalysis to
guide future biocatalyst design. Overall, the platform technology developed in TRIPase will open the door to
a wealth of new excited-state chemistry in proteins and in doing so will underpin the development of a new
generation of evolvable photocatalysts with efficiencies and specificities akin to natural enzymes.
Organisations
People |
ORCID iD |
| Anthony Green (Principal Investigator) |
Publications
Lister TM
(2025)
Engineered enzymes for enantioselective nucleophilic aromatic substitutions.
in Nature
| Description | A talk to Syngenta (Manchester) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Industry/Business |
| Results and Impact | The presentation aimed to share insights on innovative chemical research within my group and its potential future applications. The talk fostered discussions on industry collaboration, and Syngenta expressed interest in exploring related techniques for sustainable solutions. |
| Year(s) Of Engagement Activity | 2025 |
| Description | Acceptance of Blavatnik Award |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | I was named the 2025 Chemical Sciences Laureate for my group's groundbreaking discoveries in designing and engineering novel enzymes with catalytic functions previously unknown in nature. I delivered a talk showcasing our research and its broader societal impact to an invited audience of the general public. The presentation was also made available online, enabling viewers worldwide to engage with our work. |
| Year(s) Of Engagement Activity | 2024 |