Monday May 18 2009
CEA
Cyclodipeptide synthases are a family of tRNA-dependent peptide bond–forming enzymes
Nature Chem Biol (2009) 5, 414-420: Proc Natl Acad Sci USA (2009) 106, 7426-31
CEA
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 (Compound 1) pathway. Albonoursin, or cyclo(
,
-dehydroPhe-,-dehydroLeu), is an antibacterial DKP produced by Streptomyces noursei. In this pathway, the formation of the cyclo(Phe-Leu) (Compound 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).
,-dehydroPhe-,-dehydroLeu), is an antibacterial DKP produced by Streptomyces noursei. In this pathway, the formation of the cyclo(Phe-Leu) (Compound 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).Gondry M, Sauguet L, Belin P, Thai R, Amouroux R, Tellier C, Tuphile K, Jacquet M, Braud S, Courçon M, Masson C, Dubois S, Lautru S, Lecoq A, Hashimoto SI, Genet R, Pernodet JL. (2009). Cyclodipeptide synthases are a family of tRNA-dependent peptide bond-forming enzymes. Nature Chem Biol 5, 414-420.
Belin P, Le Du MH, Fielding A, Lequin O, Jacquet M, Charbonnier JB, Lecoq A, Thai R, Courçon M, Masson C, Dugave C, Genet R, Pernodet JL, Gondry M. (2009). Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis. Proc Natl Acad Sci USA. 106,7426-7431.