Activation-independent capture of free fatty acids at the bacterial cell envelope by BrtB
5 affiliations
- 1Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto, Matosinhos, Portugal
- 2Bioorganic Analytics, Institute for Inorganic and Analytical Chemistry, Friedrich Schiller University Jena, Jena, Germany
- 3Synthetic Biology of Photosynthetic Organisms, Matthias Schleiden Institute for Genetics, Bioinformatics and Molecular Botany, Friedrich Schiller University Jena, Jena, Germany
- 4Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
- 5Department of Biology, Faculty of Sciences, University of Porto, R. Campo Alegre, Porto, Portugal
Abstract
Fatty acids (FAs) are key metabolites in living organisms, shaping membrane architecture, and helping cellular acclimatization to changing conditions. Bacteria synthesize FAs de novo but can also reclaim them from membrane lipids or uptake them from the environment, usually converting free fatty acids (FFAs) into activated FAs that can then be further metabolized. In cyanobacteria, it is the acyl-acyl carrier protein synthetase (Aas) that activates exogenous FFAs. However, the cyanobacterial enzyme BrtB was recently shown to esterify, in vitro, FFAs directly onto abundant chlorinated glycolipids (bartolosides), generating bartoloside fatty acid esters (B-FAs). Whether this chemistry operates in vivo, where it occurs, and what its implications are for cell physiology have remained unclear. Here, we show that in the cyanobacterium Synechocystis salina LEGE 06099, BrtB likely esterifies exogenous FFAs at or near the cell envelope without prior activation to generate B-FAs. We found that supplemented FFAs were converted into B-FAs within minutes. Unexpectedly, this response occurred with minimal changes in gene expression and little alteration of the extracellular proteome, consistent with a pathway already in place. Additionally, we observed that B-FAs can further be hydrolyzed into hydroxybartolosides, the levels of which increase in response to FA supply, suggesting a transient sequestration of FFA. These findings identify a specific activation-independent route for the incorporation of exogenous FFAs into cyanobacterial specialized metabolites, expanding the known repertoire of bacterial FA utilization.
IMPORTANCE: Fatty acids (FAs) are essential building blocks of cell membranes and key metabolites in all living organisms. While bacteria synthesize FAs de novo, they can also incorporate exogenous FAs, saving the energetic cost of biosynthesis. Bacteria are generally thought to require their prior activation before they can be incorporated into metabolism. Here we show that a marine cyanobacterium bypasses this requirement through BrtB, which directly esterifies exogenous FAs onto specialized glycolipids in vivo without prior activation, likely at or near the cell envelope. This process occurs within minutes and is accompanied by minimal changes in gene expression, consistent with a pre-existing pathway. Our findings identify a specific activation-independent route for incorporation of exogenous FAs into cyanobacterial specialized metabolites and suggest that these glycolipids may transiently sequester FAs in response to environmental availability.
Related
- PqiABC forms a membrane-bridging conduit and mediates bidirectional phospholipid transport across the Gram-negative bacterial envelope
- Lipid droplet targeting drives substrate access during very long chain fatty acid activation by Fat1
- Brown algae produce hydrocarbons via fatty acid photodecarboxylase–dependent and fatty acid photodecarboxylase–independent pathways
- Structural and Functional Characterization of Cysteate Fatty Acyltransferases Involved in Bacterial Sulfonolipid Biosynthesis.
- Hypoxia drives asymmetric envelope remodelling to promote membrane adaptation and antibiotic tolerance in mycobacteria
BibTeX
@article{kahn2026activationindependent,
title = {{Activation-independent capture of free fatty acids at the bacterial cell envelope by BrtB}},
author = {Amaranta Kahn and Cristina I. F. Sousa and João P. A. Reis and David A. Russo and Adriana Rego and Ricardo J. C. V. Queirós and Marine Cuau and Julie A. Z. Zedler and Sandra A. C. Figueiredo and Paulo Oliveira and Pedro N. Leão},
journal = {mBio},
year = {2026},
month = sep,
doi = {10.1128/mbio.01132-26},
url = {https://doi.org/10.1128/mbio.01132-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Activation-independent capture of free fatty acids at the bacterial cell envelope by BrtB
AU - Amaranta Kahn
AU - Cristina I. F. Sousa
AU - João P. A. Reis
AU - David A. Russo
AU - Adriana Rego
AU - Ricardo J. C. V. Queirós
AU - Marine Cuau
AU - Julie A. Z. Zedler
AU - Sandra A. C. Figueiredo
AU - Paulo Oliveira
AU - Pedro N. Leão
PY - 2026
DA - 2026/09/09
JO - mBio
DO - 10.1128/mbio.01132-26
UR - https://doi.org/10.1128/mbio.01132-26
AB - Fatty acids (FAs) are key metabolites in living organisms, shaping membrane architecture, and helping cellular acclimatization to changing conditions. Bacteria synthesize FAs de novo but can also reclaim them from membrane lipids or uptake them from the environment, usually converting free fatty acids (FFAs) into activated FAs that can then be further metabolized. In cyanobacteria, it is the acyl-acyl carrier protein synthetase (Aas) that activates exogenous FFAs. However, the cyanobacterial enzyme BrtB was recently shown to esterify, in vitro, FFAs directly onto abundant chlorinated glycolipids (bartolosides), generating bartoloside fatty acid esters (B-FAs). Whether this chemistry operates in vivo, where it occurs, and what its implications are for cell physiology have remained unclear. Here, we show that in the cyanobacterium Synechocystis salina LEGE 06099, BrtB likely esterifies exogenous FFAs at or near the cell envelope without prior activation to generate B-FAs. We found that supplemented FFAs were converted into B-FAs within minutes. Unexpectedly, this response occurred with minimal changes in gene expression and little alteration of the extracellular proteome, consistent with a pathway already in place. Additionally, we observed that B-FAs can further be hydrolyzed into hydroxybartolosides, the levels of which increase in response to FA supply, suggesting a transient sequestration of FFA. These findings identify a specific activation-independent route for the incorporation of exogenous FFAs into cyanobacterial specialized metabolites, expanding the known repertoire of bacterial FA utilization. IMPORTANCE: Fatty acids (FAs) are essential building blocks of cell membranes and key metabolites in all living organisms. While bacteria synthesize FAs de novo, they can also incorporate exogenous FAs, saving the energetic cost of biosynthesis. Bacteria are generally thought to require their prior activation before they can be incorporated into metabolism. Here we show that a marine cyanobacterium bypasses this requirement through BrtB, which directly esterifies exogenous FAs onto specialized glycolipids in vivo without prior activation, likely at or near the cell envelope. This process occurs within minutes and is accompanied by minimal changes in gene expression, consistent with a pre-existing pathway. Our findings identify a specific activation-independent route for incorporation of exogenous FAs into cyanobacterial specialized metabolites and suggest that these glycolipids may transiently sequester FAs in response to environmental availability.
SN - 2150-7511
ER -