# Pyridoxal Photoenzymes for Organic Synthesis

> **NIH NIH R21** · CORNELL UNIVERSITY · 2022 · $237,149

## Abstract

7. Project Summary
 The work described in this proposal aims to advance biocatalytic tools for use in the synthesis of
medicinally valuable molecules. We will develop new reaction mechanisms for pyridoxal-dependent enzymes
to enable the facile synthesis of non-canonical amino acids through photoexcitation of pyridoxal intermediates
involved in the catalysis of threonine aldolase and serine hydroxymethyltransferase. The first goal is to
photoexcite the PLP external aldimine enabling it to function as a photoacid. This mechanism will allow these
enzymes to use a broader set of 𝛼-, 𝛽-, and 𝛾-amino acids as pronucleophiles. The second goal is to excite the
PLP-quinonoid to access a more reducing excited state. This species can reduce alkyl halides, redox-active
esters, and cyanoheterocyles to form radicals that can recombine with the PLP-quinonoid radical to produce
various non-canonical amino acids. Collectively, these studies will provide a new tool for the synthesis of non-
canonical amino acids and serve as the foundation for a new area in photoenzymatic catalysis. The methods
and the goals proposed in the Specific Aims can streamline the synthesis of biological probes and drug targets,
creating a significant benefit to human health and associated biomedical sciences.

## Key facts

- **NIH application ID:** 10426622
- **Project number:** 1R21GM146043-01
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Todd Kurt Hyster
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $237,149
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10426622

## Citation

> US National Institutes of Health, RePORTER application 10426622, Pyridoxal Photoenzymes for Organic Synthesis (1R21GM146043-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10426622. Licensed CC0.

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