(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.) > cellular organisms: NE > Bacteria: NE > Terrabacteria group: NE > Actinobacteria [phylum]: NE > Actinobacteria [class]: NE > Streptomycetales: NE > Streptomycetaceae: NE > Streptomyces: NE > unclassified Streptomyces: NE > Streptomyces sp. BC16019: NE
Molecular evidence
Database
No mutation 5 structures(e.g. : 6T6H, 6T6X, 6T6Y... more)(less) 6T6H: Crystal structure of bottromycin epimerase BotH, 6T6X: Structure of the Bottromycin epimerase BotH in complex with substrate, 6T6Y: Structure of the Bottromycin epimerase BotH in complex with Bottromycin A2, 6T6Z: Structure of the Bottromycin epimerase BotH in complex with Bottromycin-A2 derivative, 6T70: Structure of the Bottromycin epimerase BotH in complex with Bottromycin A2 derivative No kinetic
LegendThis sequence has been compared to family alignement (MSA) red => minority aminoacid blue => majority aminoacid color intensity => conservation rate title => sequence position(MSA position)aminoacid rate Catalytic site Catalytic site in the MSA MRDGNGTSRRDVFEVFSRDGTPIRGFSRPGPGETVVLVHGVAMDRRIWAE SGFLDALPDAHVLALDLRGRGESGRVGTAEGHALRRYVEDVRAVLDRFGR ARYSLFGTFFGGRIALQVAAVDTRVARAFSFCAHAEQVEIPEDAVEEEAV AVEGPGGHAYLRDHFTGRGAPPWMVEACARVDPGELGAATRGLLHGSDRR TERGHPDQELVLITADGDADLAPFHAGERRLGAHLWLVDAPTRIKAAGRL AEVGRRVAGVLAEGGHGTGDAPAEARTTGDAPAEARASGTGVV
D-amino acids endow peptides with diverse, desirable properties, but the post-translational and site-specific epimerization of L-amino acids into their D-counterparts is rare and chemically challenging. Bottromycins are ribosomally synthesized and post-translationally modified peptides that have overcome this challenge and feature a D-aspartate (D-Asp), which was proposed to arise spontaneously during biosynthesis. We have identified the highly unusual alpha/beta-hydrolase (ABH) fold enzyme BotH as a peptide epimerase responsible for the post-translational epimerization of L-Asp to D-Asp during bottromycin biosynthesis. The biochemical characterization of BotH combined with the structures of BotH and the BotH-substrate complex allowed us to propose a mechanism for this reaction. Bioinformatic analyses of BotH homologs show that similar ABH enzymes are found in diverse biosynthetic gene clusters. This places BotH as the founding member of a group of atypical ABH enzymes that may be able to epimerize non-Asp stereocenters across different families of secondary metabolites.
Streptomyces sp. BC16019 BotH bottromycin epimerase
