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This content will become publicly available on May 13, 2027

Title: AexB is an aromatic amino acid exporter that functions as a metabolic safety valve
ABSTRACT Aromatic amino acids—tryptophan, tyrosine, phenylalanine, and histidine—are essential for bacterial growth and are among the most energetically expensive metabolites to synthesize. Despite this cost, it has been recently shown that bacteria possess exporters for these amino acids. Here, we identifyaexB(formerlyyvjA) as a gene encoding a novel aromatic amino acid exporter inBacillus subtilis. Using a transposon-based screen, we found thataexBoverexpression confers resistance to the toxic tryptophan analog 5-fluorotryptophan. Additional analog screens revealed that AexB also promotes tolerance to toxic derivatives of tyrosine, phenylalanine, and histidine but not non-aromatic amino acids. LC-MS analysis showed that AexB specifically exports aromatic amino acids, and co-culture assays confirmed that overexpression ofaexBcan support the growth of aromatic amino acid auxotrophs. Furthermore, overexpression ofaexBimpaired growth when intracellular tryptophan was limiting. On the other hand, deletion ofaexBexacerbated growth defects under excess tryptophan conditions, likely due to feedback inhibition of aromatic amino acid synthesis pathways. Our findings reveal that AexB is an aromatic amino acid exporter that functions as a metabolic safety valve. IMPORTANCEIdentification and characterization of amino acid exporters is a broadly relevant topic. Amino acid synthesis is energetically costly, and thus functional relevance for their export is unintuitive. Identification of the molecular components that allow export may offer new engineering opportunities to improve biomanufacturing and metabolic engineering. Characterization of these exporters may also provide a more complete understanding of the human microbiome where amino acids, especially tryptophan, have been established as nodes of crosstalk between host and microbiota.  more » « less
Award ID(s):
2235451
PAR ID:
10686891
Author(s) / Creator(s):
;
Editor(s):
Konovalova, Anna
Publisher / Repository:
Wiley
Date Published:
Journal Name:
mBio
Volume:
17
Issue:
5
ISSN:
2150-7511
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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