lasI (PA1432) encodes the LuxI-family acyl-homoserine-lactone synthase of Pseudomonas aeruginosa (EC 2.3.1.184), a 201-residue cytoplasmic enzyme that makes the diffusible autoinducer N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL). It takes the homoserine lactone ring from S-adenosyl-L-methionine and the acyl chain from 3-oxododecanoyl-acyl carrier protein supplied by fatty acid synthesis, releasing 5'-methylthioadenosine and holo-ACP. Its crystal structure shows a GNAT-like beta-sheet platform with a V-shaped substrate cleft, an acyl-chain tunnel and an acyl-ACP binding surface. 3-oxo-C12-HSL diffuses between cells and, above a threshold concentration, binds the receptor and transcription factor LasR, which activates lasB (elastase) and other virulence genes, rhlR/rhlI, and lasI itself. LasI thus makes the signal at the top of the las quorum-sensing hierarchy; LasR receives and transduces it.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007165 signal transduction | IBA GO_REF:0000033 | MODIFY | Summary: IBA from PTN002217335 (5 leaf IBAs: lasI, rhlI, Yersinia yspI and ypeI, Bradyrhizobium bjaI), whose IBD has one seed, this gene's PseudoCAP IDA to PMID:8493556. The target appearing in its own WITH/FROM is expected. Reason: The node's leaves are LuxI-family AHL synthases. They make the diffusible signal; they do not receive or relay it. GO restricts signal transduction to events that begin with signal reception and, for signalling between cells, to the receiving cell, which here is LasR. The process these synthases do take part in is quorum sensing, whose definition includes producing the signal molecule. Other autoinducer synthases carry quorum sensing with experimental evidence (ainS G3FB25 IDA; luxS P45578 IMP). The correction is lateral: quorum sensing is not a descendant of signal transduction. Propagation Review Root cause: SOURCE BAD Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P33883 · lasI SOURCE BAD The sole seed is this gene's PseudoCAP IDA to PMID:8493556, which shows LasI makes the autoinducer (signal producer), annotated as signal transduction (a receiving-cell process). Proposed replacements: quorum sensing Supporting Evidence: PMID:8278364 A diffusible signal molecule, the P. aeruginosa autoinducer (PAI), produced by the bacterial cell and released into the growth medium, is required for activity of LasR. PMID:15306017 the acyl-homoserine lactone (AHL) synthase LasI that produces 3-oxo-C12-AHL from the substrates 3-oxo-C12-acyl-carrier protein (acyl-ACP) and S-adenosyl-L-methionine |
| GO:0007165 signal transduction | IDA PMID:8493556 Expression of Pseudomonas aeruginosa virulence genes require... | MODIFY | Summary: PseudoCAP IDA; sole seed of the PTN002217335 IBD. Passador et al. (1993) show with gene fusions that lasI is needed for high-level elastase expression and is involved in synthesis of the diffusible autoinducer PAI. Reason: The paper is right for this gene, but the term is not. The abstract shows that lasI is needed to make a diffusible signal that LasR requires, which places LasI in quorum sensing as the signal producer. It does not show LasI acting in signal transduction, which GO restricts to the receiving cell. The evidence the abstract describes is genetic (gene fusions and the mutant phenotype), so IMP may fit better than IDA; the full text was not read, so the evidence code is not challenged here. Proposed replacements: quorum sensing Supporting Evidence: PMID:8493556 Experiments with gene fusions show that gene lasl is essential for high expression of elastase. The lasl gene is involved in the synthesis of a diffusible molecule termed Pseudomonas autoinducer (PAI). |
| GO:0016740 transferase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping of IPR001690 (autoinducer synthase) to transferase activity. Reason: Correct but too general. N-acyl homoserine lactone synthase activity (GO:0061579), an is_a descendant via acyltransferase activity, is already on the gene and is directly supported. Proposed replacements: N-acyl homoserine lactone synthase activity Supporting Evidence: file:PSEAE/lasI/lasI-uniprot.txt InterPro; IPR001690; Autoind_synthase. |
| GO:0061579 N-acyl homoserine lactone synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from the EC 2.3.1.184 / Rhea:10096 assignment. Reason: Core activity. Purified LasI made 3-oxo-C12-HSL from acyl-ACP and SAM in a reconstituted system (PMID:12480888), and the crystal structure shows the substrate sites. GOA has only this electronic row for the activity; an experimental (IDA) row to PMID:12480888 would also give the PTN002217335 node an experimental MF anchor. Supporting Evidence: PMID:12480888 An in vitro fatty acid-3-oxo-AHL synthesis system was established utilizing purified P. aeruginosa Fab proteins, ACP and the LasI 3-oxo-AHL synthase. PMID:15306017 the acyl-homoserine lactone (AHL) synthase LasI that produces 3-oxo-C12-AHL from the substrates 3-oxo-C12-acyl-carrier protein (acyl-ACP) and S-adenosyl-L-methionine |
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Download this section (compressed HTML)Q: Should LuxI-family AHL synthases, as signal producers, be annotated to GO:0009372 quorum sensing rather than GO:0007165 signal transduction across PANTHER PTHR39322? The same family-level signal transduction annotation also reaches RhlI, LuxI and TraI by IBA or TreeGrafter IEA.
Q: Is a dedicated process term for N-acyl homoserine lactone biosynthesis wanted in GO, or is GO:0061579 plus quorum sensing enough?
Experiment: Determine steady-state kinetics of purified LasI with 3-oxo-C12-ACP versus 3-oxo-C12-CoA and shorter acyl-ACPs, to quantify acyl-donor and chain-length specificity in vitro.
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