If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
|Superclasses:||Biosynthesis → Secondary Metabolites Biosynthesis → Autoinducer Biosynthesis|
Cell-to-cell communication in bacteria is accomplished through the exchange of extracellular signaling molecules called autoinducers. This process, termed quorum sensing, allows bacterial populations to coordinate gene expression as a function of cell density. Many processes benefit from community cooperation, including bioluminescence, virulence factor expression, antibiotic production and biofilm development.
Cell to cell signaling through quorum sensing in bacteria occurs through three main processes LuxR-LuxI, LuxS/AI-2, and AI-3/epinephrine/norepinephrine. The LuxR-LuxI process controls signaling through autoinducer 1 (AI-1) which is an N-acyl-homoserine lactone (AHL). It was first described in Vibrio fischeri as a regulator of bioluminescence. However Escherichia coli and Salmonella typhimurium lack LuxI and do not synthesize AHLs, although the product of gene sdiA recognizes AHLs from other bacterial species. The LuxS/AI-2 process controls both intraspecies and interspecies signaling. It was first described as an extracellular signal produced by the marine bacterium Vibrio harveyi to control luciferase expression [Bassler94, Surette99]. In E. coli and Salmonella typhimurium AI-2 activates transcription of the lsr operon encoding an ABC transporter, the LsrB subunit of which binds AI-2 (see autoinducer-2 ABC transporter). The AI-3/epinephrine/norepinephrine process involves recognition by gut commensals of autoinducer produced by self, other bacteria, or human hormones. In E. coli AI-3 interacts with a membrane-bound protein QseC which is part of the QseB-QseC two component system.
AI-2 production depends upon growth conditions. Factors include nutrients, pH, osmolarity, oxygen, growth rate and stress factors. However, its exact role in cell signaling is still controversial and there is evidence that its function may be metabolic [Gonzalez06, Herzberg06, Wang05a]. A role for AI-2 in pathogenesis also remains to be established although transcriptomics studies have suggested that AI-2 may have a role in the regulation of virulence in enterohemorrhagic E. coli [Bansal08]. The E. coli AI-2 network has also been the subject of different modeling approaches [Gonzalez10, Li06].
Review: Kendall, M.M. and V. Sperandio (2009) "Cell-to-Cell Signaling in Escherichia coli and Salmonella." EcoSal 5.5 [ECOSAL]
About This Pathway
One of the main bacterial autoinducers is autoinducer 2 (AI-2) which mediates the quorum sensing 2 (QS-2) system. Its biosynthesis is catalyzed by the LuxS enzyme which also participates in the SAM cycle (see S-adenosyl-L-methionine cycle I). The LuxS enzyme is found in many bacteria including E. coli and Salmonella typhimurium. Its role in AI-2 biosynthesis is suggested by the presence of the Lsr ABC transporter, the LsrB protein of which serves as the AI-2 receptor in many of these organisms [Rezzonico08] (see autoinducer-2 ABC transporter).
The precursor of AI-2 is synthesized by the enzyme S-ribosylhomocysteine lyase, which also catalyzes a step in the SAM cycle. The enzyme converts S-ribosyl-L-homocysteine to L-homocysteine and 4,5-dihydroxy-2,3-pentanedione. Within the SAM cycle, the main product of the enzyme is L-homocysteine. In AI-2 biosynthesis 4,5-dihydroxy-2,3-pentanedione is of major importance as it appears to be nonenzymatically converted in a series of chemical modifications to the mature autoinducer.
The exact nature of the chemical transformations depends on the species. In E. coli and most pathogenic bacteria that form AI-2 the spontaneous transformations include cyclization to (2R,4S)-2-methyl-2,4-dihydroxydihydrofuran-3-one and hydration to the final autoinducer (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran. This form of the autoinducer, which was first characterized from Salmonella typhimurium, was shown to be different from the form that was initially described from Vibrio harveyi (see below) and is recognized by the LsrB periplasmic binding protein [Miller04].
Members of the order Vibrionales produce a different form of the autoinducer. In those organisms, 4,5-dihydroxy-2,3-pentanedione appears to form a different stereoisomer, namely (2S,4S)-2-methyl-2,4-dihydroxydihydrofuran-3-one, which hydrates to (2S,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran and forms a complex with a borate ion to form (2S,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran-borate [Chen02, Rezzonico08], (see MetaCyc pathway autoinducer AI-2 biosynthesis II (Vibrio)). The mechanism that controls which stereoisomer is formed is still not understood.
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