A different function for a member of an ancient and highly conserved cytochrome P450 family: From essential sterols to plant defense

*Department of Metabolic Biology, John Innes Centre, Norwich NR4 7UH, United Kingdom;
^‡Institute of Grassland and Environmental Research, Aberystwyth SY23 3EB, Wales, United Kingdom;
^§School of Biological Sciences and School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich NR4 7TJ, United Kingdom;
^¶Institute of Food Research, Norwich NR4 7UA, United Kingdom;
^‖Institute of Plant Molecular Biology, Centre National de la Recherché Scientifique–Unite Propre de Recherché 2357, Universite Louis Pasteur, 67000 Strasbourg, France; and
^†Laboratory of Photosynthesis and Environmental Molecular Physiology, Institute of Botany, Chinese Academy of Sciences, Nanxincun 20, Fragrance Hill, Beijing 100093, China

Edited by Klaus Hahlbrock, Max Planck Institute for Plant Breeding Research, Cologne, Germany, and approved October 10, 2006 (received for review September 7, 2006)

Abstract

CYP51 sterol demethylases are the only cytochrome P450 enzymes with a conserved function across the animal, fungal, and plant kingdoms (in the synthesis of essential sterols). These highly conserved enzymes, which are important targets for cholesterol-lowering drugs, antifungal agents, and herbicides, are regarded as the most ancient member cytochrome P450 family. Here we present a report of a CYP51 enzyme that has acquired a different function. We show that the plant enzyme AsCYP51H10 is dispensable for synthesis of essential sterols and has been recruited for the production of antimicrobial compounds (avenacins) that confer disease resistance in oats. The AsCyp51H10 gene is synonymous with Sad2, a gene that we previously had defined by mutation as being required for avenacin synthesis. In earlier work, we showed that Sad1, the gene encoding the first committed enzyme in the avenacin pathway (β-amyrin synthase), had arisen by duplication and divergence of a cycloartenol synthase-like gene. Together these data indicate an intimate evolutionary connection between the sterol and avenacin pathways. Sad1 and Sad2 lie within 70 kb of each other and are expressed specifically in the epidermal cells of the root tip, the site of accumulation of avenacins. These findings raise intriguing questions about the recruitment, coevolution, and regulation of the components of this specialized defense-related metabolic pathway.

Footnotes

**To whom correspondence should be addressed. E-mail: anne.osbourn{at}bbsrc.ac.uk
Author contributions: X.Q., F.M., D.W.-R., H.S., and A.O. designed research; X.Q., S.B., B.Q., M.L., A.H., F.M., J.E., H.S., A.L., and R.M. performed research; X.Q. and S.B. contributed new reagents/analytic tools; X.Q., S.B., B.Q., A.H., F.M., J.E., D.W.-R., H.S., A.L., R.M., and A.O. analyzed data; and X.Q. and A.O. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS direct submission.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. DQ680849–DQ680854).
Freely available online through the PNAS open access option.