title: Strategies for engineering plant natural products: the iridoid-derived monoterpene indole alkaloids of Catharanthus roseus.
abstract: The manipulation of pathways to make unnatural variants of natural compounds, a process often termed combinatorial biosynthesis, has been robustly successful in prokaryotic systems. The development of approaches to generate new-to-nature compounds from plant-based pathways is, in comparison, much less advanced. Success will depend on the specific chemistry of the pathway, as well as on the suitability of the plant system for transformation and genetic manipulation. As plant pathways are elucidated, and can be heterologously expressed in hosts that are more amenable to genetic manipulation, biosynthetic production of new-to-nature compounds from plant pathways will become more widespread. In this chapter, some of the key strategies that have been developed for metabolic engineering of plant pathways, namely directed biosynthesis, mutasynthesis, and pathway incorporation of engineered enzymes are highlighted. The iridoid-derived monoterpene indole alkaloids from C. roseus, which are the focus of this chapter, provide an excellent system for developing these strategies.
authors.affiliation: John Innes Centre, Department of Biological Chemistry, Norwich Research Park, Norwich, United Kingdom. sarah.o'connor@jic.ac.uk
authors.forename: Sarah E
authors.initials: SE
authors.lastname: O'Connor
mesh_terms: D001688:Biological Products / Q000378:metabolism*; D053898:Biosynthetic Pathways; D019759:Carbon-Nitrogen Lyases / Q000235:genetics / Q000378:metabolism; D030008:Catharanthus / Q000235:genetics / Q000378:metabolism*; D003470:Culture Media / Q000378:metabolism; D026121:Indole Alkaloids / Q000378:metabolism*; D057888:Iridoid Glucosides / Q000378:metabolism; D039823:Iridoids / Q000378:metabolism*; D060847:Metabolic Engineering / Q000379:methods*; D039821:Monoterpenes / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D014363:Tryptamines / Q000378:metabolism; D014748:Vinca Alkaloids / Q000378:metabolism
chemical_list: D001688:Biological Products; D003470:Culture Media; D026121:Indole Alkaloids; D057888:Iridoid Glucosides; D039823:Iridoids; D039821:Monoterpenes; D010940:Plant Proteins; D014363:Tryptamines; D014748:Vinca Alkaloids; C021086:secologanin; C030820:tryptamine; D019759:Carbon-Nitrogen Lyases; C022684:strictosidine synthetase; C017836:catharanthine