# The chemoenzymatic synthesis of daptomycin analogs

> **NIH NIH R03** · UNIVERSITY OF OKLAHOMA · 2020 · $71,613

## Abstract

Structural modification of natural products through the addition of various chemical groups onto the
natural product skeleton is an attractive strategy to develop pharmacologically active molecules with
differing properties. However, the structural complexities of several macrocyclic peptide natural products
present significant challenges in their chemical modification. Herein, we propose to exploit the inherent
promiscuity of a tryptophan modifying enzyme CdpNPT to structurally modify a macrocyclic peptide drug,
daptomycin and generate analogs with potential enhanced activities. Specifically, we intend to generate
20-30 new daptomycin analogs via our innovative chemoenzymatic platform that includes the synthesis
of diverse array of alkyl-pyrophosphate analogs as alkyl donors. The new daptomycin analogs will then
be structurally characterized and screened for antibacterial potency against a representative set of
bacterial strains including daptomycin resistant strains. The outcome of this study is expected to provide
a systematic SAR on the size and type of attachment of chemical groups on daptomycin as a means to
generate improved daptomycin analogs with enhanced antibacterial activity.

## Key facts

- **NIH application ID:** 9928894
- **Project number:** 5R03AI141950-02
- **Recipient organization:** UNIVERSITY OF OKLAHOMA
- **Principal Investigator:** Shanteri Singh
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $71,613
- **Award type:** 5
- **Project period:** 2019-05-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928894

## Citation

> US National Institutes of Health, RePORTER application 9928894, The chemoenzymatic synthesis of daptomycin analogs (5R03AI141950-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9928894. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*