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.
Department of Chemistry and School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA.
Gang
G
Zhao
Wei
W
Wan
Shahrzad
S
Mansouri
Joshua F
JF
Alfaro
Bonnie L
BL
Bassler
Kenneth A
KA
Cornell
Zhaohui Sunny
ZS
Zhou
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