Structural highlights
Function
ALBA_STRNR Involved in the biosynthesis of albonoursin (cyclo[(alpha,beta-dehydro-Phe)-(alpha,beta-dehydro-Leu)]), an antibacterial peptide. Catalyzes the formation of alpha,beta-dehydro-Phe (DPhe) and alpha,beta-dehydro-Leu (DLeu) residues during the biosynthesis of albonoursin. The catalytic reaction of cyclo(L-Phe-L-Leu) occurs in a two-step sequential alpha-beta-dehydrogenation leading first to cyclo(alpha,beta-dehydro-Phe-L-Leu) and finally to albonoursin. Can also use cyclo(L-Phe-L-His), cyclo(L-Trp-L-Trp), cyclo(L-Leu-L-Ala), cyclo(L-Phe-Gly), cyclo(L-Leu-Gly), cyclo(L-Ser-Gly) and cyclo(L-Glu-Gly) as substrate suggesting that the diketopiperazine ring is essential for the enzymatic reaction.[1] [2]
Publication Abstract from PubMed
Modified cyclic dipeptides represent a widespread class of secondary metabolites with diverse pharmacological activities, including antibacterial, antifungal, and antitumor. Here, we report the structural characterization of the Streptomyces noursei enzyme AlbAB, a cyclodipeptide oxidase (CDO) carrying out alpha,beta-dehydrogenations during the biosynthesis of the antibiotic albonoursin. We show that AlbAB is a megadalton heterooligomeric enzyme filament containing covalently bound flavin mononucleotide cofactors. We highlight that AlbAB filaments consist of alternating dimers of AlbA and AlbB and that enzyme activity is crucially dependent on filament formation. We show that AlbA-AlbB interactions are highly conserved suggesting that other CDO-like enzymes are likely enzyme filaments. As CDOs have been employed in the structural diversification of cyclic dipeptides, our results will be useful for future applications of CDOs in biocatalysis and chemoenzymatic synthesis.
Cyclodipeptide oxidase is an enzyme filament.,Andreas MP, Giessen TW Nat Commun. 2024 Apr 27;15(1):3574. doi: 10.1038/s41467-024-48030-9. PMID:38678027[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gondry M, Lautru S, Fusai G, Meunier G, Ménez A, Genet R. Cyclic dipeptide oxidase from Streptomyces noursei. Isolation, purification and partial characterization of a novel, amino acyl alpha,beta-dehydrogenase. Eur J Biochem. 2001 Mar;268(6):1712-21. PMID:11248691 doi:10.1046/j.1432-1033.2001.02038.x
- ↑ Lautru S, Gondry M, Genet R, Pernodet JL. The albonoursin gene Cluster of S noursei biosynthesis of diketopiperazine metabolites independent of nonribosomal peptide synthetases. Chem Biol. 2002 Dec;9(12):1355-64. PMID:12498889
- ↑ Andreas MP, Giessen TW. Cyclodipeptide oxidase is an enzyme filament. Nat Commun. 2024 Apr 27;15(1):3574. PMID:38678027 doi:10.1038/s41467-024-48030-9
