# Characterization of polyamine biosynthetic enzymes from human gut microbes associated with colon and pancreatic cancer

> **NIH NIH R16** · FORT LEWIS COLLEGE · 2023 · $162,500

## Abstract

PROJECT SUMMARY
Polyamine biosynthesis in human cancer cells is a long-standing therapeutic target. Accumulating evidence
suggests that polyamine production by gut microbes contributes to 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
development kinetic and structural models describing the function of both carboxyspermidine dehydrogenase
and carboxyspermidine decarboxylase in major gut constituents from the Bacteroides and Clostridium genera.
These aims serve as a necessary precursor to a future program of mechanism-guided drug design. The long-
term goal of this work is to open new avenues for the treatment of colorectal and pancreatic cancer. Interestingly,
the genes of predicted polyamine biosynthetic enzymes from many gut genera appear to encode redundant
paths toward the production of spermidine. We hypothesize that these paths are not redundant, but generate
unique polyamine products. We propose the use of LC-TQ-MS assays to delineate the polyamine products from
apparently redundant enzyme pairs found in Clostridium. Spermidine synthase is a key focus of this aim because
the prokaryotic orthologs of this enzyme have been shown to produce a variety of polyamine products besides
spermidine. This work will expand our fundamental understanding of the functional variations found within a key
gut microbe metabolic pathway: polyamine biosynthesis.

## Key facts

- **NIH application ID:** 10664019
- **Project number:** 5R16GM146714-02
- **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:** $162,500
- **Award type:** 5
- **Project period:** 2022-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10664019

## Citation

> US National Institutes of Health, RePORTER application 10664019, Characterization of polyamine biosynthetic enzymes from human gut microbes associated with colon and pancreatic cancer (5R16GM146714-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10664019. Licensed CC0.

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