# Expanding the synthetic utility of enzymes

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $451,757

## Abstract

PROJECT SUMMARY
Achieving selectivity in complexity-building transformations is critical for being able to access target molecules
with potential to impact human health such has potential drugs and chemical probes for studying biological
systems. Although significant strides have been made in developing chemical methods for complexity-building
reactions, it often remains challenging to carry out these transformations with high levels of chem-, site- and
stereoselectivity on complex or functional group dense molecules. In contrast to small molecule catalysts and
reagents, enzymes often have evolved to carry out reactions with high levels of selectivity. The discovery of
specific enzymatic reactions and development of the utility of these catalysts has the potential to enable to
synthetic strategies and grant us access to new molecules with potent biological activity. This proposal
describes several strategies for developing robust enzyme-mediated reactions and leveraging these tools for
the streamlined synthesis of molecules with pharmaceutical potential.
The goal of this NIGMS proposal is to provide synthetic chemists with highly selective, efficient, well-
characterized and sustainable biocatalytic methods to be planned into synthetic approaches toward target
molecules. Using enzymes from natural product biosynthetic pathways and targeted protein families as a
starting point, we will elucidate the natural chemical function and mechanism of a given enzyme. From this
initial benchmark, we use bioinformatic tools, structural analysis, computational modeling, and evolutionary
approaches to assemble panels of complementary biocatalysts of utility to the synthetic community. We
subsequently seek to use the platform provided by each protein class to design new reactions and apply these
methods to the streamlined synthesis of molecules relevant to human health. My group seeks biocatalytic
solutions to reactions that continue to challenge modern synthetic chemists including selective C–H
hydroxylation, site- and stereoselective oxidative dearomatization, and the chemo- and stereoselective
derivatization of a-amino acids. Moving forward, we continue to work in these areas and are seeking to
develop biocatalytic C–C bond forming reactions, C–H functionalization reactions beyond hydroxylation, and
strategies for building and elaborating functional group dense molecules such as nucleotides.
In summary, this proposal describes the development of chemo-, site- and stereoselective transformations
mediated by enzymes. These methods will directly enable the synthesis of complex biologically active
molecules relevant to human health.

## Key facts

- **NIH application ID:** 10896277
- **Project number:** 5R35GM124880-08
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Alison Narayan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $451,757
- **Award type:** 5
- **Project period:** 2017-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896277

## Citation

> US National Institutes of Health, RePORTER application 10896277, Expanding the synthetic utility of enzymes (5R35GM124880-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10896277. Licensed CC0.

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