Cytochrome P450-mediated metabolic engineering: current progress and future challenges.
Cytochromes P450 catalyze a broad range of regiospecific, stereospecific and irreversible steps in the biosynthetic routes of plant natural metabolites with important applications in pharmaceutical, cosmetic, fragrance and flavour, or polymer industries. They are consequently essential drivers for the engineered bioproduction of such compounds. Two ground-breaking developments of commercial products driven by the engineering of P450s are the antimalarial drug precursor artemisinic acid and blue roses or carnations. Tedious optimizations were required to generate marketable products. Hurdles encountered in P450 engineering and their potential solutions are summarized here. Together with recent technical developments and novel approaches to metabolic engineering, the lessons from this pioneering work should considerably boost exploitation of the amazing P450 toolkit emerging from accelerated sequencing of plant genomes.
Institute of Plant Molecular Biology of CNRS UPR2357, University of Strasbourg, F-67084 Strasbourg, France; Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Germany.
Hugues
H
Renault
Department of Plant and Environmental Sciences, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Copenhagen, Denmark.
Jean-Etienne
JE
Bassard
Department of Plant and Environmental Sciences, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Copenhagen, Denmark.
Björn
B
Hamberger
Institute of Plant Molecular Biology of CNRS UPR2357, University of Strasbourg, F-67084 Strasbourg, France; Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Germany; University of Strasbourg Institute for Advanced Study (USIAS), France. Electronic address: werck@unistra.fr.
Danièle
D
Werck-Reichhart
D037621:Artemisinins / Q000378:metabolism; D003116:Color; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D035264:Flowers; D060847:Metabolic Engineering
D037621:Artemisinins; C047721:artemisic acid; D003577:Cytochrome P-450 Enzyme System