# Stopped-flow spectrometer for analysis of reaction kinetics

> **NIH NIH R16** · FORT LEWIS COLLEGE · 2023 · $94,530

## Abstract

PROJECT SUMMARY
Polyamine biosynthesis in human cancer cells is a long-standing therapeutic target. Accumulating evidence
suggests that polyamine production by gut microbes modulates the progression of colon and pancreatic cancer.
Biosynthesis of the polyamine spermidine by gut bacteria follows a pathway distinct from the human pathway
making this bacterial pathway a unique drug target. The two central enzymes in this pathway, carboxyspermidine
dehydrogenase and carboxyspermidine decarboxylase, have received only limited characterization. We propose
to solve the first structure of a carboxyspermidine dehydrogenase and to develop kinetic and structural models
describing the function of both carboxyspermidine dehydrogenase and carboxyspermidine decarboxylase in
major gut constituents from the Bacteroides and Clostridium genera. Both carboxyspermidine dehydrogenase
and decarboxylase use coenzymes with unique spectroscopic “handles” that can be interrogated by stopped-
flow spectrometry to discern the kinetic steps of their respective catalytic cycles. A thorough structural and
functional understanding of enzyme mechanisms is a necessary precursor to mechanism-guided drug design.
This work will expand our fundamental understanding of a key gut microbe metabolic pathway: polyamine
biosynthesis.

## Key facts

- **NIH application ID:** 10796272
- **Project number:** 3R16GM146714-02S1
- **Recipient organization:** FORT LEWIS COLLEGE
- **Principal Investigator:** Jeffrey S McFarlane
- **Activity code:** R16 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $94,530
- **Award type:** 3
- **Project period:** 2022-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10796272

## Citation

> US National Institutes of Health, RePORTER application 10796272, Stopped-flow spectrometer for analysis of reaction kinetics (3R16GM146714-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10796272. Licensed CC0.

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