Plate Nº 30 · recorded October 10, 2026
Biology & EvolutionReported finding
Scientists identify first PLP-dependent tRNA-modifying enzyme
Scientists have identified AvaS, the first enzyme known to use a vitamin B6 derivative to modify transfer RNA in bacteria. The discovery in Pseudomonas aeruginosa opens a new chapter in RNA biology.
By Marcus Bennett3 min read540 words
In brief
- The enzyme AvaS was identified as the first PLP-dependent enzyme known to modify tRNA, published September 9 in Nature Chemical Biology.
- The ava²C modification was detected in Pseudomonas aeruginosa, Acinetobacter baumannii, Vibrio cholerae, and the plant Arabidopsis thaliana.
- AvaS converts lysidine (k²C) into ava²C using PLP, a vitamin B6 derivative previously linked only to amino acid metabolism.
- ava²C helps bacteria read genetic code faster and adapt to metabolic and oxidative stress, including antibiotic exposure.
- The research was led by SMART AMR with collaborators from MIT, Nanyang Technological University, and institutions in the US, Poland, and France.
Researchers have identified the first pyridoxal phosphate (PLP)-dependent enzyme known to modify transfer RNA in bacteria, according to a paper published September 9 in Nature Chemical Biology.
The enzyme, called aminovaleramididine synthetase (AvaS), was found in Pseudomonas aeruginosa, a bacterium that causes pneumonia and sepsis. The discovery establishes an entirely new class of tRNA-modifying enzymes and assigns PLP-dependent enzymes an unexpected role in RNA chemistry.
Why does this matter for antibiotic resistance?
Bacteria develop resistance through strategies that depend on controlling which proteins they make, when they make them, and how accurately. Transfer RNAs, or tRNAs, function as molecular delivery vehicles, ferrying chemical "stickers" that regulate protein production in response to stress, including exposure to antibiotics.
The new modification, called aminovaleramide cytidine (ava²C), helps bacteria read genetic code more quickly and efficiently, the researchers reported. It also helps them adapt to metabolic and oxidative stress, conditions that include exposure to antibiotic drugs.
How did the team find AvaS?
The work was led by SMART AMR, the Antimicrobial Resistance interdisciplinary research group within the Singapore-MIT Alliance for Research and Technology. Collaborators came from MIT, Nanyang Technological University in Singapore, and institutions in the United States, Poland, and France.
Using SMART's high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform, the team systematically screened thousands of P. aeruginosa mutants and identified AvaS. They also confirmed that ava²C exists in other organisms:
- The bacteria Acinetobacter baumannii and Vibrio cholerae
- The plant Arabidopsis thaliana
"While many RNA modifications have been known for decades, researchers are still uncovering the full extent of their roles," said Professor Peter Dedon, co-lead principal investigator at SMART AMR, professor of biological engineering at MIT, and a co-corresponding author of the paper.
"The discovery of AvaS opens a previously unknown chapter in RNA biology," Dedon added.
What does the enzyme actually do?
AvaS converts lysidine (k²C), a previously documented tRNA modification, into ava²C. That conversion marks the first time a PLP-dependent enzyme has been tied directly to tRNA modification. PLP, a derivative of vitamin B6, had previously been linked only to amino acid metabolism.
The finding expands the known chemical mechanisms bacteria use to regulate protein production, which had previously included methylation, thiolation, and isomerisation. It also gives PLP-dependent enzymes a new biological function: directly modifying tRNA rather than working only on metabolic pathways.
"Our discovery has revealed, for the first time, that PLP-dependent enzymes can directly modify tRNA, expanding our knowledge and understanding of RNA-modifying chemistry," said Jingjing Sun, research scientist at SMART AMR, first author, and co-corresponding author of the paper.
What comes next?
The SMART AMR team plans to study how ava²C affects bacterial stress responses and metabolism, and how the modification can be disrupted or prevented. Future work may also examine whether other organisms use similar tools to build specific chemical modifications, and how ava²C shapes protein production beyond bacteria.
The research is preliminary, and any therapeutic application remains far off. The team noted that more unknown RNA-modifying enzymes likely await discovery, a process the group's epitranscriptomics platform is built to accelerate.
Funding came from the National Research Foundation Singapore through its Campus for Research Excellence and Technological Enterprise program.
via smart.mit.edu (Original)
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