# Expanding the biosynthetic mechanisms of natural antimicrobial peptides

> **NIH NIH R21** · UNIV OF MARYLAND, COLLEGE PARK · 2024 · $185,726

## Abstract

Project Summary
The recent interest in developing alternatives to traditional antibiotics are driving timely investments that are
urgently needed to confront the growing antimicrobial resistance crisis. Fortuitously, the burgeoning microbial
genomics era has revitalized efforts to explore natural products (NPs) as key sources of new antibiotics and their
alternatives. However, tapping NPs as therapeutics requires a sophisticated understanding of biosynthetic
mechanisms, the instructions of which are frequently encoded within discrete biosynthetic gene clusters (BGCs).
Antimicrobial peptides (AMPs), a diverse class of NPs that are widely produced across evolution, are intensively
being researched as an antibiotic alternative, especially because AMPs rapidly kill bacteria and that resistance
to AMPs has been slow to emerge. Here, we aim to build upon the recent discovery of an AMP family, of which
the corresponding BGC is unlike previously recognized BGCs for AMPs. Moreover, this AMP family and its BGC
are widespread throughout diverse bacteria, which represents a rich resource of AMPs to exploit for future
therapeutic development. Thus, to advance these efforts, the overarching goal of this project is to dissect the
mechanisms of this novel BGC that leads to AMP production. Using a combination of molecular biology
techniques, bacterial genetic approaches, and biochemical assays, we will focus on ascribing roles of the BGC
components to 1) biosynthetic events that yield the mature AMP product and 2) the regulatory phenomena that
may be needed to balance AMP yield against fitness costs to the producer. Our results will provide key
knowledge that will serve as the basis for future sophisticated biochemical examinations, empower genome
mining and bioengineering of this AMP class, advance future efforts that seek to optimize yields for cost-effective
manufacturing of this AMP family in sufficient quantities for preclinical and clinical studies, and in designing
strategies to prevent or subvert the rise of resistance to this AMP family.

## Key facts

- **NIH application ID:** 10983898
- **Project number:** 1R21AI178268-01A1
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Seth Wayne Dickey
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $185,726
- **Award type:** 1
- **Project period:** 2024-06-07 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10983898

## Citation

> US National Institutes of Health, RePORTER application 10983898, Expanding the biosynthetic mechanisms of natural antimicrobial peptides (1R21AI178268-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10983898. Licensed CC0.

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