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- W4313894984 abstract "Photosynthetic organelles offer attractive features for engineering small molecule bioproduction by their ability to convert solar energy into chemical energy required for metabolism. The possibility to couple biochemical production directly to photosynthetic assimilation as a source of energy and substrates has intrigued metabolic engineers. Specifically, the chemical diversity found in plants often relies on cytochrome P450-mediated hydroxylations that depend on reductant supply for catalysis and which often lead to metabolic bottlenecks for heterologous production of complex molecules. By directing P450 enzymes to plant chloroplasts one can elegantly deal with such redox prerequisites. In this study, we explore the capacity of the plant photosynthetic machinery to drive P450-dependent formation of the indigo precursor indoxyl-β-D-glucoside (indican) by targeting an engineered indican biosynthetic pathway to tobacco (Nicotiana benthamiana) chloroplasts. We show that both native and engineered variants belonging to the human CYP2 family are catalytically active in chloroplasts when driven by photosynthetic reducing power and optimize construct designs to improve productivity. However, while increasing supply of tryptophan leads to an increase in indole accumulation, it does not improve indican productivity, suggesting that P450 activity limits overall productivity. Co-expression of different redox partners also does not improve productivity, indicating that supply of reducing power is not a bottleneck. Finally, in vitro kinetic measurements showed that the different redox partners were efficiently reduced by photosystem I but plant ferredoxin provided the highest light-dependent P450 activity. This study demonstrates the inherent ability of photosynthesis to support P450-dependent metabolic pathways. Plants and photosynthetic microbes are therefore uniquely suited for engineering P450-dependent metabolic pathways regardless of enzyme origin. Our findings have implications for metabolic engineering in photosynthetic hosts for production of high-value chemicals or drug metabolites for pharmacological studies." @default.
- W4313894984 created "2023-01-10" @default.
- W4313894984 creator A5022237765 @default.
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- W4313894984 creator A5071783725 @default.
- W4313894984 date "2023-01-09" @default.
- W4313894984 modified "2023-10-03" @default.
- W4313894984 title "Exploiting photosynthesis-driven P450 activity to produce indican in tobacco chloroplasts" @default.
- W4313894984 cites W1495151627 @default.
- W4313894984 cites W1604244147 @default.
- W4313894984 cites W1606239426 @default.
- W4313894984 cites W166401860 @default.
- W4313894984 cites W1975288527 @default.
- W4313894984 cites W1980361506 @default.
- W4313894984 cites W1980783983 @default.
- W4313894984 cites W1981407107 @default.
- W4313894984 cites W1982287089 @default.
- W4313894984 cites W1988923572 @default.
- W4313894984 cites W1991463968 @default.
- W4313894984 cites W1994692225 @default.
- W4313894984 cites W1996687916 @default.
- W4313894984 cites W1998256050 @default.
- W4313894984 cites W2003117374 @default.
- W4313894984 cites W2010244877 @default.
- W4313894984 cites W2014935712 @default.
- W4313894984 cites W2017002927 @default.
- W4313894984 cites W2021966348 @default.
- W4313894984 cites W2028463525 @default.
- W4313894984 cites W2031187931 @default.
- W4313894984 cites W2038886711 @default.
- W4313894984 cites W2040057010 @default.
- W4313894984 cites W2042702851 @default.
- W4313894984 cites W2043236952 @default.
- W4313894984 cites W2057668454 @default.
- W4313894984 cites W2057986258 @default.
- W4313894984 cites W2060687391 @default.
- W4313894984 cites W2066820270 @default.
- W4313894984 cites W2072893741 @default.
- W4313894984 cites W2075727429 @default.
- W4313894984 cites W2078880422 @default.
- W4313894984 cites W2089741482 @default.
- W4313894984 cites W2090303381 @default.
- W4313894984 cites W2091943391 @default.
- W4313894984 cites W2107410272 @default.
- W4313894984 cites W2111492898 @default.
- W4313894984 cites W2112110544 @default.
- W4313894984 cites W2117201020 @default.
- W4313894984 cites W2117851178 @default.
- W4313894984 cites W2120797114 @default.
- W4313894984 cites W2124019798 @default.
- W4313894984 cites W2144263923 @default.
- W4313894984 cites W2145147173 @default.
- W4313894984 cites W2158717672 @default.
- W4313894984 cites W2160845184 @default.
- W4313894984 cites W2164380925 @default.
- W4313894984 cites W2210713843 @default.
- W4313894984 cites W2234528424 @default.
- W4313894984 cites W2238393485 @default.
- W4313894984 cites W2255189041 @default.
- W4313894984 cites W2311798020 @default.
- W4313894984 cites W2328286101 @default.
- W4313894984 cites W2334381352 @default.
- W4313894984 cites W2344094488 @default.
- W4313894984 cites W2444500095 @default.
- W4313894984 cites W2501269559 @default.
- W4313894984 cites W2523360402 @default.
- W4313894984 cites W2610594245 @default.
- W4313894984 cites W2730775751 @default.
- W4313894984 cites W2760694286 @default.
- W4313894984 cites W2770501663 @default.
- W4313894984 cites W2783523019 @default.
- W4313894984 cites W2793117809 @default.
- W4313894984 cites W2801399898 @default.
- W4313894984 cites W2894479533 @default.
- W4313894984 cites W2900091042 @default.
- W4313894984 cites W2923516433 @default.
- W4313894984 cites W2944601004 @default.
- W4313894984 cites W2953371585 @default.
- W4313894984 cites W2955235905 @default.
- W4313894984 cites W2982260601 @default.
- W4313894984 cites W2987429045 @default.
- W4313894984 cites W2990866481 @default.
- W4313894984 cites W2995733572 @default.
- W4313894984 cites W3007806612 @default.
- W4313894984 cites W3018232545 @default.
- W4313894984 cites W3025076413 @default.
- W4313894984 cites W3035847987 @default.
- W4313894984 cites W3040351768 @default.
- W4313894984 cites W3047946645 @default.
- W4313894984 cites W3083572654 @default.
- W4313894984 cites W3111702746 @default.
- W4313894984 cites W3119362894 @default.
- W4313894984 cites W3153199601 @default.
- W4313894984 cites W3153587730 @default.
- W4313894984 cites W3167877219 @default.
- W4313894984 cites W3173903422 @default.