Chemical synthesis of S-ribosyl-L-homocysteine and activity assay as a LuxS substrate.
Bacterial quorum sensing is mediated by autoinducers, small signaling molecules generated by bacteria. It has been proposed that the LuxS enzyme converts S-ribosyl-L-homocysteine to 4,5-dihydroxy-2,3-pentanedione, the precursor of autoinducer 2 (AI-2). We report here a chemical synthesis of S-ribosyl-L-homocysteine and its analogue using Mitsunobu coupling. Chemically synthesized ribosylhomocysteine has been confirmed as a substrate for LuxS in both an enzyme assay and a whole cell quorum sensing assay. The chemical entities of products from the LuxS reaction were also established. Several ribosylhomocysteine analogues have been tested as LuxS inhibitors.
Zhao
Gang
G
Department of Chemistry and School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA.
Wan
Wei
W
Mansouri
Shahrzad
S
Alfaro
Joshua F
JF
Bassler
Bonnie L
BL
Cornell
Kenneth A
KA
Zhou
Zhaohui Sunny
ZS
D001412:Bacillus subtilis / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D013437:Carbon-Sulfur Lyases; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism*; D007700:Kinetics; D013379:Substrate Specificity
D001426:Bacterial Proteins; C487472:S-ribosyl-L-homocysteine; D006710:Homocysteine; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria