# Investigations of lanthipeptides derived from human gut microbiome

> **NIH NIH F32** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2022 · $29,155

## Abstract

Project Summary/Abstract
 The emergence of antibiotic resistance poses a serious global threat of growing concern to human, animal
and environmental health. Therefore, there is an urgent need to discover alternative sources of new antibiotics
to combat pathogenic infections while limiting the emergence of bacterial resistance. The van der Donk group
focuses on the study of lanthipeptides, a class of ribosomally synthesized and posttranslationally modified
peptide (RiPP) natural products characterized by lanthionine and methyllanthionine rings that have potential as
novel pharmaceuticals and antimicrobial agents. Indeed, the lanthipeptide nisin has been utilized by the U.S.
food industry as a preservative to combat food-borne pathogens for more than 50 years with little to no
development of bacterial resistance. The human microbiome is a rich source of novel RiPP-like secondary
metabolites with potent antimicrobial properties. However, the identities of nearly all these natural products are
unknown, and their biological roles are poorly understood. Thus, a deeper analysis of human microbiome-derived
natural products would not only lead to the discovery of new antimicrobial compounds but also guide new
therapies that seek to modulate the human microbiota in order to impact human health. Through genome mining,
three novel Clostridiales RiPP biosynthetic gene clusters (BGC) from Lachnospiraceae bacterium C6A11 (lah),
Clostridium indicum (cli) and Clostridium sp. AF15-17LB (cls) were identified. Lachnospiraceae bacterium C6A11
colonizes the human gut and other Lachnospiraceae bacterium are linked to type 2 diabetes, and resistance to
gut colonization by Clostridium difficile - a leading cause of nosocomial antibiotic-associated diarrhea. The BGCs
are unique in that they encode an intriguing constellation of posttranslational modification enzymes (PTM) in
conjunction with several distinct precursor peptides from which the natural products are derived. However, the
identities of all these natural products are unknown and their biosynthesis poorly understood. Therefore, the
research proposed herein is designed to examine all three BGCs by first developing a new generally applicable
platform for accessing these natural products from E. coli and/or C. sporogenes for characterization and
bioactivity screening. In addition, the role of each PTM enzyme will be examined through systematic gene
deletions. The structure-function relationships of the PTM enzymes will be examined via protein crystallography
and a subset will be bioengineered towards new functionalities. Completion of the proposed research will lead
to the discovery of up to eleven novel RiPP natural products with potential therapeutic applications/interventions
and the development of a new generally applicable platform for accessing other RiPP-like natural products from
the human gut microbiome. In addition, the findings from this research will provide a platform of tools, knowledge
and techniques...

## Key facts

- **NIH application ID:** 10557782
- **Project number:** 5F32GM140621-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Richard Selorm Ayikpoe
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $29,155
- **Award type:** 5
- **Project period:** 2021-09-16 → 2023-02-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10557782

## Citation

> US National Institutes of Health, RePORTER application 10557782, Investigations of lanthipeptides derived from human gut microbiome (5F32GM140621-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10557782. Licensed CC0.

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