Evolution of acyl-substrate recognition by a family of acyl-homoserine lactone synthases.
Members of the LuxI protein family catalyze synthesis of acyl-homoserine lactone (acyl-HSL) quorum sensing signals from S-adenosyl-L-methionine and an acyl thioester. Some LuxI family members prefer acyl-CoA, and others prefer acyl-acyl carrier protein (ACP) as the acyl-thioester substrate. We sought to understand the evolutionary history and mechanisms mediating this substrate preference. Our phylogenetic and motif analysis of the LuxI acyl-HSL synthase family indicates that the acyl-CoA-utilizing enzymes evolved from an acyl-ACP-utilizing ancestor. To further understand how acyl-ACPs and acyl-CoAs are recognized by acyl-HSL synthases we studied BmaI1, an octanoyl-ACP-dependent LuxI family member from Burkholderia mallei, and BjaI, an isovaleryl-CoA-dependent LuxI family member from Bradyrhizobium japonicum. We synthesized thioether analogs of their thioester acyl-substrates to probe recognition of the acyl-phosphopantetheine moiety common to both acyl-ACP and acyl-CoA substrates. The kinetics of catalysis and inhibition of these enzymes indicate that they recognize the acyl-phosphopantetheine moiety and they recognize non-preferred substrates with this moiety. We find that CoA substrate utilization arose through exaptation of acyl-phosphopantetheine recognition in this enzyme family.
Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
Quin H
QH
Christensen
Department of Chemistry and Biochemistry, Boise State University, Boise, Idaho, United States of America.
Ryan M
RM
Brecht
Department of Chemistry and Biochemistry, Boise State University, Boise, Idaho, United States of America.
Dastagiri
D
Dudekula
Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
E Peter
EP
Greenberg
Department of Chemistry and Biochemistry, Boise State University, Boise, Idaho, United States of America.
Rajesh
R
Nagarajan
D054742:Acyl-Butyrolactones / Q000737:chemistry / Q000378:metabolism*; D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D005075:Biological Evolution; D007700:Kinetics; D008958:Models, Molecular; D010802:Phylogeny; D056510:Position-Specific Scoring Matrices; D011485:Protein Binding; D011487:Protein Conformation; D013379:Substrate Specificity; D014157:Transcription Factors / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*
D054742:Acyl-Butyrolactones; D001426:Bacterial Proteins; C085427:LuxI protein, Bacteria; D014157:Transcription Factors