# Redefining fatty acid degradation by Staphylococcus aureus

> **NIH NIH R21** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2021 · $229,500

## Abstract

PROJECT SUMMARY/ABSTRACT
 Bacteria require fatty acids for a variety of biological functions, including the construction of
phospholipids. Staphylococcus aureus, like other bacteria, synthesize fatty acids using a fatty acid biosynthesis
pathway referred to as FASII, but can also scavenge fatty acids from the environment using the recently
described Fak pathway. In addition to fatty acid biosynthesis and acquisition, it is common for bacteria to degrade
fatty acids using fatty acid degradation (Fad) enzymes. In some cases, this is to adjust chain length but also
occurs for -oxidation of fatty acids for energy generation. S. aureus does not perform -oxidation of fatty acids
and has been thought to not possess the capacity to degrade fatty acids. This is due, in part, to the absence of
a key crotonase enzyme. This is surprising considering that S. aureus is annotated to encode all the other
necessary Fad enzymes, though their function has not been confirmed. During RNAseq studies of the Fak
pathway, we observed an ~17-fold increased expression of the group of genes annotated to encode Fad
proteins. Indeed, no crotonase enzyme was apparent, though all the other Fad functionalities were annotated.
Using bioinformatics, we identified a putative crotonase enzyme in S. aureus that we now call FadB based on
nomenclature in other systems. When expressed with S. aureus FabA, the S. aureus FadB can functionally
complement an E. coli fadAB mutant on minimal media with fatty acid as a sole carbon source. This demonstrates
that 1) S. aureus FadB can substitute for the E. coli crotonase activity-containing enzyme, and 2) S. aureus does
possess a complete Fad pathway and likely can degrade fatty acids. We seek to characterize this pathway using
two complementary Specific Aims.
 Aim 1 uses the E. coli model to confirm the identity of the other S. aureus Fad proteins and to define the
activity of S. aureus FadB, including the substrate range in a well-described system with the benefit of minimal
media. We found that under rich media conditions (there is no minimal media for S. aureus) that the S. aureus
Fad pathway is lowly expressed and it is unknown if these genes are co-transcribed. Aim 2 determines the
genetic context of the Fad-encoding genes. In addition, Aim 2 examines the ability for S. aureus to degrade fatty
acids using controlled expression of the Fad genes by a combination of radio-labelled fatty acids and mass
spectrometry approaches.
 The Fad-encoding genes have been identified in a variety of transcriptomic studies, but remain unstudied
likely due to the known dogma in the field that S. aureus does not possess a complete Fad pathway and cannot
degrade fatty acids. We anticipate that the completion of this application will redefine fatty acid metabolism in S.
aureus and determine for the first time that S. aureus can degrade fatty acids. This will change how the field
understands S. aureus metabolism and will set the stage for future applications e...

## Key facts

- **NIH application ID:** 10173634
- **Project number:** 5R21AI153773-02
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Jeffrey Lee Bose
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $229,500
- **Award type:** 5
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10173634

## Citation

> US National Institutes of Health, RePORTER application 10173634, Redefining fatty acid degradation by Staphylococcus aureus (5R21AI153773-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10173634. Licensed CC0.

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