ATP-dependent hydroxylation of an unactivated primary carbon with water.

Autor:	Jacoby C; Microbiology, Faculty of Biology, Albert-Ludwigs-Universität Freiburg, Schänzlestr. 1, 79104, Freiburg, Germany., Ferlaino S; Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany., Bezold D; Institute of Organic Chemistry, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104, Freiburg, Germany., Jessen H; Institute of Organic Chemistry, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104, Freiburg, Germany., Müller M; Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany., Boll M; Microbiology, Faculty of Biology, Albert-Ludwigs-Universität Freiburg, Schänzlestr. 1, 79104, Freiburg, Germany. matthias.boll@biologie.uni-freiburg.de.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2020 Aug 06; Vol. 11 (1), pp. 3906. Date of Electronic Publication: 2020 Aug 06.
DOI:	10.1038/s41467-020-17675-7
Abstrakt:	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.
Databáze:	MEDLINE
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