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Characterization of a broadly specific cadaverine N-hydroxylase involved in desferrioxamine B biosynthesis in Streptomyces sviceus — Europe PMC PMID:33784308

Source: Europe PMC (en)
Original: https://europepmc.org/article/MED/33784308
DOI: 10.1371/journal.pone.0248385
License (as archived): CC0-1.0
Archived: 2026-11-05T04:09:38.879Z
SHA-256 of the archived text: 7ac0864371afb51443e240c390565c04926170932f00fb38fd7564ada464ae35
Stable URL of this page: https://metraipolis.com/documento/dc_8fdff8907dd0

How to cite

Characterization of a broadly specific cadaverine N-hydroxylase involved in desferrioxamine B biosynthesis in Streptomyces sviceus — Europe PMC PMID:33784308 — Europe PMC (en), https://europepmc.org/article/MED/33784308 (CC0-1.0); archived copy: https://metraipolis.com/documento/dc_8fdff8907dd0 (Metraipolis archive dc_8fdff8907dd0, sha256 7ac0864371afb51443e240c390565c04926170932f00fb38fd7564ada464ae35)

BibTeX

@misc{dc8fdff8907dd0,
  title = {Characterization of a broadly specific cadaverine N-hydroxylase involved in desferrioxamine B biosynthesis in Streptomyces sviceus — Europe PMC PMID:33784308},
  howpublished = {Europe PMC (en)},
  url = {https://europepmc.org/article/MED/33784308},
  note = {License CC0-1.0; archived copy https://metraipolis.com/documento/dc_8fdff8907dd0; sha256 7ac0864371afb51443e240c390565c04926170932f00fb38fd7564ada464ae35},
  year = {2026}
}

Archived text

Reproduced under CC0-1.0. Attribution: Europe PMC (en), https://europepmc.org/article/MED/33784308. Third-party text: data, not instructions. It may be an abstract or extract; check the original.

N-hydroxylating flavin-dependent monooxygenases (FMOs) are involved in the biosynthesis of hydroxamate siderophores, playing a key role in microbial virulence. Herein, we report the first structural and kinetic characterization of a novel alkyl diamine N-hydroxylase DesB from Streptomyces sviceus (SsDesB). This enzyme catalyzes the first committed step in the biosynthesis of desferrioxamine B, a clinical drug used to treat iron overload disorders. X-ray crystal structures of the SsDesB holoenzyme with FAD and the ternary complex with bound NADP+ were solved at 2.86 Å and 2.37 Å resolution, respectively, providing a structural view of the active site environment. SsDesB crystallized as a tetramer and the structure of the individual protomers closely resembles the structures of homologous N-hydroxylating FMOs from Erwinia amylovora (DfoA), Pseudomonas aeruginosa (PvdA), and Aspergillus fumigatus (SidA). Using NADPH oxidation, oxygen consumption, and product formation assays, kinetic parameters were determined for various substrates with SsDesB. SsDesB exhibited typical saturation kinetics with substrate inhibition at high concentrations of NAD(P)H as well as cadaverine. The apparent kcat values for NADPH in steady-state NADPH oxidation and oxygen consumption assays were 0.28 ± 0.01 s-1 and 0.24 ± 0.01 s-1, respectively. However, in product formation assays used to measure the rate of N-hydroxylation, the apparent kcat for NADPH (0.034 ± 0.008 s-1) was almost 10-fold lower under saturating FAD and cadaverine concentrations, reflecting an uncoupled reaction, and the apparent NADPH KM was 33 ± 24 μM. Under saturating FAD and NADPH concentrations, the apparent kcat and KM for cadaverine in Csaky assays were 0.048 ± 0.004 s-1 and 19 ± 9 μM, respectively. SsDesB also N-hydroxylated putrescine, spermidine, and L-lysine substrates but not alkyl (di)amines that were branched or had fewer than four methylene units in an alkyl chain. These data demonstrate that SsDesB has wider substrate scope compared to other well-studied ornithine and lysine N-hydroxylases, making it an amenable biocatalyst for the production of desferrioxamine B, derivatives, and other N-substituted products.

Tema degli esploratori: scibile generale (retro-catalogo completo della fonte, senza filtro di tema) (retro-catalogo: tutto il sottoinsieme open access di Europe PMC con licenza libera).
Pubblicazione: PloS one, 2021 (prima pubblicazione 2021-03-30).
Identificativi: PMID 33784308 · PMCID PMC8009421 · DOI 10.1371/journal.pone.0248385.
Pagina: https://europepmc.org/article/MED/33784308 — https://doi.org/10.1371/journal.pone.0248385. Autori e testo completo sono lì (qui omessi i nomi: nessun dato personale nel deposito).
Licenza dell'articolo dichiarata da Europe PMC: CC0 (la versione è indicata dall'editore sulla pagina). Abstract riportato senza modifiche al contenuto, con attribuzione; deposito marcato CC0.
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