ATP-dependent hydroxylation of an unactivated primary carbon with water.
Adenosine Triphosphate
/ metabolism
Anaerobiosis
Bacterial Proteins
/ genetics
Betaproteobacteria
/ genetics
Carbon
/ chemistry
Cholestadienols
/ chemistry
Cholesterol
/ chemistry
Genes, Bacterial
Hydro-Lyases
/ genetics
Hydroxylation
Mixed Function Oxygenases
/ genetics
Models, Biological
Oxidation-Reduction
Phylogeny
Recombinant Proteins
/ genetics
Water
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 08 2020
06 08 2020
Historique:
received:
06
03
2020
accepted:
09
07
2020
entrez:
9
8
2020
pubmed:
9
8
2020
medline:
22
9
2020
Statut:
epublish
Résumé
Enzymatic hydroxylation of unactivated primary carbons is generally associated with the use of molecular oxygen as co-substrate for monooxygenases. However, in anaerobic cholesterol-degrading bacteria such as Sterolibacterium denitrificans the primary carbon of the isoprenoid side chain is oxidised to a carboxylate in the absence of oxygen. Here, we identify an enzymatic reaction sequence comprising two molybdenum-dependent hydroxylases and one ATP-dependent dehydratase that accomplish the hydroxylation of unactivated primary C26 methyl group of cholesterol with water: (i) hydroxylation of C25 to a tertiary alcohol, (ii) ATP-dependent dehydration to an alkene via a phosphorylated intermediate, (iii) hydroxylation of C26 to an allylic alcohol that is subsequently oxidised to the carboxylate. The three-step enzymatic reaction cascade divides the high activation energy barrier of primary C-H bond cleavage into three biologically feasible steps. This finding expands our knowledge of biological C-H activations beyond canonical oxygenase-dependent reactions.
Identifiants
pubmed: 32764563
doi: 10.1038/s41467-020-17675-7
pii: 10.1038/s41467-020-17675-7
pmc: PMC7411048
doi:
Substances chimiques
Bacterial Proteins
0
Cholestadienols
0
Recombinant Proteins
0
Water
059QF0KO0R
Carbon
7440-44-0
Adenosine Triphosphate
8L70Q75FXE
Cholesterol
97C5T2UQ7J
Mixed Function Oxygenases
EC 1.-
Hydro-Lyases
EC 4.2.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3906Références
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