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B6db references: 32483377

type Journal Article
authors Cui Z, Overbay J, Wang X, Liu X, Zhang Y, Bhardwaj M, Lemke A, Wiegmann D, Niro G, Thorson JS, Ducho C, Van Lanen SG
title Pyridoxal-5'-phosphate-dependent Alkyl Transfer in Nucleoside Antibiotic Biosynthesis
journal Nat Chem Biol
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ui 32483377
year (2020)
pages in press
keywords doi: 10.1038/s41589-020-0548-3
abstract Several nucleoside antibiotics are structurally characterized by a 5″-amino-5″-deoxyribose (ADR) appended via a glycosidic bond to a high-carbon sugar nucleoside (5'S,6'S)-5'-C-glycyluridine (GlyU). GlyU is further modified with an N-alkylamine linker, the biosynthetic origin of which has yet to be established. By using a combination of feeding experiments with isotopically labeled precursors and characterization of recombinant proteins from multiple pathways, the biosynthetic mechanism for N-alkylamine installation for ADR-GlyU-containing nucleoside antibiotics has been uncovered. The data reveal S-adenosyl-L-methionine (AdoMet) as the direct precursor of the N-alkylamine, but, unlike conventional AdoMet- or decarboxylated AdoMet-dependent alkyltransferases, the reaction is catalyzed by a pyridoxal-5'-phosphate-dependent aminobutyryltransferase (ABTase) using a stepwise γ-replacement mechanism that couples γ-elimination of AdoMet with aza-γ-addition onto the disaccharide alkyl acceptor. In addition to using a conceptually different strategy for AdoMet-dependent alkylation, the newly discovered ABTases require a phosphorylated disaccharide alkyl acceptor, revealing a cryptic intermediate in the biosynthetic pathway.
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last changed 2020/06/03 15:38

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