Highly conserved progesterone 5 beta-reductase genes (P5 beta R) from 5 beta-cardenolide-free and 5 beta-cardenolide-producing angiosperms

Bauer P, Munkert J, Brydziun M, Burda E, Mueller-Uri F, Gröger H, Muller YA, Kreis W (2010)
PHYTOCHEMISTRY 71(13): 1495-1505.

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Abstract
Most cardenolides used in the therapy of cardiac insufficiency are 5 beta-configured and thus the stereo-specific reduction of the Delta(4,5)-double bond of a steroid precursor is a crucial step in their biosynthesis. This step is thought to be catalysed by progesterone 5 beta-reductases. We report here on the isolation of 11 progesterone 5 beta-reductase (P5 beta R) orthologues from 5 beta-cardenolide-free and 5 beta-cardenolide-producing plant species belonging to five different angiosperm orders (Brassicales, Gentianales, Lamiales, Malvales and Solanales). Amino acid sequences of the P5 beta R described here were highly conserved. They all contain certain motifs qualifying them as members of a class of stereo-selective enone reductases capable of reducing activated C=C double bonds by a 1,4-addition mechanism. Protein modeling revealed seven conserved amino acids in the substrate-binding/catalytic site of these enzymes which are all supposed to exhibit low substrate specificity. Eight P5 beta R genes isolated were expressed in Escherichia coli. Recombinant enzymes reduced progesterone stereo-specifically to 5 beta-pregane-3,20-dione. The progesterone 5 beta-reductases from Digitalis canariensis and Arabidopsis thaliana reduced activated C=C double bonds of molecules much smaller than progesterone. The specific role of progesterone 5 beta-reductases of P5 beta Rs in cardenolide metabolism is challenged because this class of enone reductases is widespread in higher plants, and they accept a wide range of enone substrates. (C) 2010 Elsevier Ltd. All rights reserved.
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Bauer P, Munkert J, Brydziun M, et al. Highly conserved progesterone 5 beta-reductase genes (P5 beta R) from 5 beta-cardenolide-free and 5 beta-cardenolide-producing angiosperms. PHYTOCHEMISTRY. 2010;71(13):1495-1505.
Bauer, P., Munkert, J., Brydziun, M., Burda, E., Mueller-Uri, F., Gröger, H., Muller, Y. A., et al. (2010). Highly conserved progesterone 5 beta-reductase genes (P5 beta R) from 5 beta-cardenolide-free and 5 beta-cardenolide-producing angiosperms. PHYTOCHEMISTRY, 71(13), 1495-1505.
Bauer, P., Munkert, J., Brydziun, M., Burda, E., Mueller-Uri, F., Gröger, H., Muller, Y. A., and Kreis, W. (2010). Highly conserved progesterone 5 beta-reductase genes (P5 beta R) from 5 beta-cardenolide-free and 5 beta-cardenolide-producing angiosperms. PHYTOCHEMISTRY 71, 1495-1505.
Bauer, P., et al., 2010. Highly conserved progesterone 5 beta-reductase genes (P5 beta R) from 5 beta-cardenolide-free and 5 beta-cardenolide-producing angiosperms. PHYTOCHEMISTRY, 71(13), p 1495-1505.
P. Bauer, et al., “Highly conserved progesterone 5 beta-reductase genes (P5 beta R) from 5 beta-cardenolide-free and 5 beta-cardenolide-producing angiosperms”, PHYTOCHEMISTRY, vol. 71, 2010, pp. 1495-1505.
Bauer, P., Munkert, J., Brydziun, M., Burda, E., Mueller-Uri, F., Gröger, H., Muller, Y.A., Kreis, W.: Highly conserved progesterone 5 beta-reductase genes (P5 beta R) from 5 beta-cardenolide-free and 5 beta-cardenolide-producing angiosperms. PHYTOCHEMISTRY. 71, 1495-1505 (2010).
Bauer, Peter, Munkert, Jennifer, Brydziun, Margareta, Burda, Edyta, Mueller-Uri, Frieder, Gröger, Harald, Muller, Yves A., and Kreis, Wolfgang. “Highly conserved progesterone 5 beta-reductase genes (P5 beta R) from 5 beta-cardenolide-free and 5 beta-cardenolide-producing angiosperms”. PHYTOCHEMISTRY 71.13 (2010): 1495-1505.
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7 Citations in Europe PMC

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Progesterone 5β-reductase genes of the Brassicaceae family as function-associated molecular markers.
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PMID: 26108256
Iridoid synthase activity is common among the plant progesterone 5β-reductase family.
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Lindner S, Geu-Flores F, Brase S, Sherden NH, O'Connor SE., Chem. Biol. 21(11), 2014
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An alternative route to cyclic terpenes by reductive cyclization in iridoid biosynthesis.
Geu-Flores F, Sherden NH, Courdavault V, Burlat V, Glenn WS, Wu C, Nims E, Cui Y, O'Connor SE., Nature 492(7427), 2012
PMID: 23172143
Toxic cardenolides: chemical ecology and coevolution of specialized plant-herbivore interactions.
Agrawal AA, Petschenka G, Bingham RA, Weber MG, Rasmann S., New Phytol. 194(1), 2012
PMID: 22292897

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