Cyclodipeptide synthases are a family of tRNA-dependent peptide bond-forming enzymes.
Cyclodipeptides and their derivatives belong to the diketopiperazine (DKP) family, which is comprised of a broad array of natural products that exhibit useful biological properties. In the few known DKP biosynthetic pathways, nonribosomal peptide synthetases (NRPSs) are involved in the synthesis of cyclodipeptides that constitute the DKP scaffold, except in the albonoursin (1) pathway. Albonoursin, or cyclo(alpha,beta-dehydroPhe-alpha,beta-dehydroLeu), is an antibacterial DKP produced by Streptomyces noursei. In this pathway, the formation of the cyclo(Phe-Leu) (2) intermediate is catalyzed by AlbC, a small protein unrelated to NRPSs. We demonstrated that AlbC uses aminoacyl-tRNAs as substrates to catalyze the formation of the DKP peptide bonds. Moreover, several other bacterial proteins, presenting moderate similarity to AlbC, also use aminoacyl-tRNAs to synthesize various cyclodipeptides. Therefore, AlbC and these related proteins belong to a newly defined family of enzymes that we have named cyclodipeptide synthases (CDPSs).
Commissariat à l'Energie Atomique, Institut de Biologie et Technologies de Saclay, Service d'Ingénierie Molé culaire des Protéines, Gif-sur-Yvette, France. muriel.gondry@cea.fr
Muriel
M
Gondry
Ludovic
L
Sauguet
Pascal
P
Belin
Robert
R
Thai
Rachel
R
Amouroux
Carine
C
Tellier
Karine
K
Tuphile
Mickaël
M
Jacquet
Sandrine
S
Braud
Marie
M
Courçon
Cédric
C
Masson
Steven
S
Dubois
Sylvie
S
Lautru
Alain
A
Lecoq
Shin-ichi
S
Hashimoto
Roger
R
Genet
Jean-Luc
JL
Pernodet
D055162:Biocatalysis; D008969:Molecular Sequence Data; D010453:Peptide Synthases / Q000737:chemistry / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism*; D013302:Streptomyces / Q000201:enzymology; D013379:Substrate Specificity
D012343:RNA, Transfer; D010453:Peptide Synthases