# Cryptic bacterial carrier proteins bridging fatty acid synthase

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $158,980

## Abstract

Project Summary. Until recently, sphingolipids within the microbial environment have been attributed to host
association, as the conventional wisdom was that bacteria did not contain their own biosynthetic pathways to
produce them. Recently, members of our team uncovered a new bacterial sphingolipid pathway involving an acyl
carrier protein similar to that of fatty acid synthase (FAS). This new acyl carrier protein, AcpSP, appears to play
a role distinct from its FAS progenitor, AcpP, whose primary purpose lies in de novo fatty acid synthesis.
Remarkably, AcpSP shares less than 30% sequence identity to AcpP, suggesting a unique activity and
interaction landscape than that of AcpP. We have identified AcpSP and serine palmitoyltransferase (SPT) within
in many pathogenic bacteria, including Neisseria gonorrhoeae, Escherichia coli (studied herein), Staphylococcus
aureus, Listeria monocytogenes, Salmonella typhimurium and Pseudomonas aeruginosa, indicating that this
pathway may be involved in pathogenesis. In this program, our team applies a suite of chemical and structural
biology tools originally developed for the study of AcpP in order to explore the interaction of AcpSP with its
partner enzymes. Using a combination of chemical probes and structure-based methods, we will characterize
the interface between AcpSP and SPT, the first key step in sphingolipid biosynthesis. To further explore the
cryptic interactions between sphingolipid biosynthesis and FAS, we will deploy a systems-wide structural
analysis to detail AcpSP interactions with de novo FAS enzymes. This program provides an essential step toward
understanding bacterial sphingolipid biosynthesis and its role in pathogenesis and will likely provide important
new targets for future drug discovery.

## Key facts

- **NIH application ID:** 10889481
- **Project number:** 1R21AI180648-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Michael D. Burkart
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $158,980
- **Award type:** 1
- **Project period:** 2024-03-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889481

## Citation

> US National Institutes of Health, RePORTER application 10889481, Cryptic bacterial carrier proteins bridging fatty acid synthase (1R21AI180648-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10889481. Licensed CC0.

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