# Protein-Protein Interactions in Natural Product Biosynthesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $12,887

## Abstract

Project Summary
This project aims to develop a new synthetic tool to investigate the ligand·protein and
protein·protein interactions in carrier protein-dependent biosynthetic pathways including fatty acid
synthase (FAS), polyketide synthase (PKS), and non-ribosomal peptide synthetase pathways
(NRPS). The natural products produced from these pathways constitute a majority of therapeutics
ranging from antibiotics and antifungals to anticancer compounds. Manipulating and controlling
the biosynthesis of these pathways toward the production of new bioactive compounds has been
a long-term goal of the field. Developing an understanding of the protein·protein interactions will
allow us to make strides toward these long-term goals, as interactions between the carrier protein
and partner protein domains guide the processivity and reactivity of the pathway. In the Burkart
lab, we have previously developed chemical biology tools to study snapshots of these interactions
or visualize them through the use of fluorescent dyes. It is proposed in this project to create a new
site-specific 15N isotopically labeled tool that will be able to visualize changes in the environment
of the ligand attached to the carrier protein and give information about chain flipping of this
prosthetic arm through 15N nuclear magnetic resonance (NMR) studies. This tool will be able to
mimic the native prosthetic arm while giving real time feedback on the temporal location of the
probe and its structural surroundings in a simplified form. This versatile tool will be able to give
information on ligand·protein interactions and chain flipping phenomena in multiple systems
through its adaptable synthetic route including Escherichia coli AcpP with the chain-length specific
LipB, and with the functional group specific ketoreductase and enoyl reductase E. coli FAS
domains.

## Key facts

- **NIH application ID:** 10249686
- **Project number:** 3R01GM095970-09S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Michael D. Burkart
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $12,887
- **Award type:** 3
- **Project period:** 2012-03-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249686

## Citation

> US National Institutes of Health, RePORTER application 10249686, Protein-Protein Interactions in Natural Product Biosynthesis (3R01GM095970-09S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10249686. Licensed CC0.

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