# Understanding the specificity and non-native catalytic activity of PLP-dependent enzymes

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA SANTA BARBARA · 2024 · $108,352

## Abstract

Project Summary
 PLP-dependent enzymes are one of the most versatile biocatalysts and catalyze a diverse range of
chemical transformations. They are widespread in nature and play critical roles in metabolism and numerous
cellular processes. Studying PLP enzymes is hence important for us to understand biology and develop
therapeutics. Because of their exquisite and versatile catalytic activity, PLP-dependent enzymes are also
remarkable biocatalysts to build diverse structurally complex and bioactive natural products; and are
indispensable biocatalytic tools for asymmetric synthesis of noncanonical amino acids and chiral amine
pharmaceuticals. However, despite the vast number of PLP-dependent enzymes characterized to date, our
abilities to predict, manipulate, and harness their activities are still largely limited. This research program desires
to fill the knowledge gap by integrating discovery, mechanistic investigation, and biocatalytic application to
systematically and comprehensively study four types of carbon-carbon (C-C) bond forming and cleaving PLP
enzymes, including our recently discovered PLP-dependent Mannich cyclase. These enzymes represent the
frontier of PLP enzymology because of their unusual activity, complementary synthetic utility to existing
biocatalysts, and unexpected evolutionary relationship with well-characterized PLP enzyme family. All proposed
aims are supported by strong preliminary data gathered in our laboratory. Our overarching goal is to understand
the chemical and substrate specificity and leverage this understanding to uncover previously unknown functions
of PLP-dependent enzymes and explore their non-native catalytic utility. Ultimately, the proposed research will
expand our mechanistic understanding on PLP enzymology, shed new light on metabolism, and provide novel
biocatalytic tools for amino acid biosynthesis.

## Key facts

- **NIH application ID:** 11033366
- **Project number:** 3R35GM151205-01S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA BARBARA
- **Principal Investigator:** Yang Hai
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $108,352
- **Award type:** 3
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11033366

## Citation

> US National Institutes of Health, RePORTER application 11033366, Understanding the specificity and non-native catalytic activity of PLP-dependent enzymes (3R35GM151205-01S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/11033366. Licensed CC0.

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