A new synthetic biology approach allows transfer of an entire metabolic pathway from a medicinal plant to a biomass crop.
Artemisinin-based therapies are the only effective treatment for malaria, the most devastating disease in human history. To meet the growing demand for artemisinin and make it accessible to the poorest, an inexpensive and rapidly scalable production platform is urgently needed. Here we have developed a new synthetic biology approach, combinatorial supertransformation of transplastomic recipient lines (COSTREL), and applied it to introduce the complete pathway for artemisinic acid, the precursor of artemisinin, into the high-biomass crop tobacco. We first introduced the core pathway of artemisinic acid biosynthesis into the chloroplast genome. The transplastomic plants were then combinatorially supertransformed with cassettes for all additional enzymes known to affect flux through the artemisinin pathway. By screening large populations of COSTREL lines, we isolated plants that produce more than 120 milligram artemisinic acid per kilogram biomass. Our work provides an efficient strategy for engineering complex biochemical pathways into plants and optimizing the metabolic output.
Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam-Golm, Germany.
Paulina
P
Fuentes
Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam-Golm, Germany.
Fei
F
Zhou
Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam-Golm, Germany.
Alexander
A
Erban
Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam-Golm, Germany.
Daniel
D
Karcher
Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam-Golm, Germany.
Joachim
J
Kopka
Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam-Golm, Germany.
Ralph
0000-0001-7502-6940
R
Bock
D000962:Antimalarials / Q000378:metabolism; D037621:Artemisinins / Q000378:metabolism; D060847:Metabolic Engineering / Q000379:methods*; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008967:Molecular Biology / Q000379:methods*; D030821:Plants, Genetically Modified / Q000235:genetics / Q000378:metabolism; D010946:Plants, Medicinal / Q000235:genetics / Q000378:metabolism*; D058615:Synthetic Biology / Q000379:methods*; D014026:Nicotiana / Q000235:genetics / Q000378:metabolism*
D000962:Antimalarials; D037621:Artemisinins; C047721:artemisic acid
Nicotiana tabacum; artemisinin; biochemistry; combinatorial transformation; metabolic engineering; plant biology; plastid transformation; synthetic biology