title: Redirecting photosynthetic reducing power toward bioactive natural product synthesis.
abstract: In addition to the products of photosynthesis, the chloroplast provides the energy and carbon building blocks required for synthesis of a wealth of bioactive natural products of which many have potential uses as pharmaceuticals. In the course of plant evolution, energy generation and biosynthetic capacities have been compartmentalized. Chloroplast photosynthesis provides ATP and NADPH as well as carbon sources for primary metabolism. Cytochrome P450 monooxygenases (P450s) in the endoplasmic reticulum (ER) synthesize a wide spectrum of bioactive natural products, powered by single electron transfers from NADPH. P450s are present in low amounts, and the reactions proceed relatively slowly due to limiting concentrations of NADPH. Here we demonstrate that it is possible to break the evolutionary compartmentalization of energy generation and P450-catalyzed biosynthesis, by relocating an entire P450-dependent pathway to the chloroplast and driving the pathway by direct use of the reducing power generated by photosystem I in a light-dependent manner. The study demonstrates the potential of transferring pathways for structurally complex high-value natural products to the chloroplast and directly tapping into the reducing power generated by photosynthesis to drive the P450s using water as the primary electron donor.
authors: Center for Synthetic Biology and Villum Research Centre "Pro-Active Plants", †Section for Molecular Plant Biology, ‡Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen , Thorvaldsensvej 40, DK-1871 Frederiksberg C, Copenhagen, Denmark.
authors: Agnieszka Zygadlo
authors: AZ
authors: Nielsen
authors: Bibi
authors: B
authors: Ziersen
authors: Kenneth
authors: K
authors: Jensen
authors: Lærke Münter
authors: LM
authors: Lassen
authors: Carl Erik
authors: CE
authors: Olsen
authors: Birger Lindberg
authors: BL
authors: Møller
authors: Poul Erik
authors: PE
authors: Jensen
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001688:Biological Products / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism; D002736:Chloroplasts / Q000201:enzymology / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004579:Electron Transport; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D008027:Light; D060847:Metabolic Engineering; D009249:NADP / Q000378:metabolism; D009570:Nitriles / Q000737:chemistry / Q000378:metabolism; D010788:Photosynthesis; D045331:Photosystem I Protein Complex / Q000378:metabolism; D010944:Plants / Q000378:metabolism*; D014026:Nicotiana / Q000378:metabolism
chemical_list: D001688:Biological Products; D009570:Nitriles; D045331:Photosystem I Protein Complex; D009249:NADP; D002244:Carbon; D000255:Adenosine Triphosphate; D003577:Cytochrome P-450 Enzyme System; C011220:dhurrin