Light-driven cytochrome P450 hydroxylations
Research output: Contribution to journal › Letter › Research › peer-review
Standard
Light-driven cytochrome P450 hydroxylations. / Jensen, Kenneth; Jensen, Poul Erik; Møller, Birger Lindberg.
In: A C S Chemical Biology, Vol. 6, No. 6, 2011, p. 533-539.Research output: Contribution to journal › Letter › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Light-driven cytochrome P450 hydroxylations
AU - Jensen, Kenneth
AU - Jensen, Poul Erik
AU - Møller, Birger Lindberg
PY - 2011
Y1 - 2011
N2 - Plants are light-driven "green" factories able to synthesize more than 200,000 different bioactive natural products, many of which are high-value products used as drugs (e.g., artemisinin, taxol, and thapsigargin). In the formation of natural products, cytochrome P450 (P450) monooxygenases play a key role in catalyzing regio- and stereospecific hydroxylations that are often difficult to achieve using the approaches of chemical synthesis. P450-catalyzed monooxygenations are dependent on electron donation typically from NADPH catalyzed by NADPH-cytochrome P450 oxidoreductase (CPR). The consumption of the costly cofactor NADPH constitutes an economical obstacle for biotechnological in vitro applications of P450s. This bottleneck has been overcome by the design of an in vitro system able to carry out light-driven P450 hydroxylations using photosystem I (PSI) for light harvesting and generation of reducing equivalents necessary to drive the P450 catalytic cycle. The in vitro system is based on the use of isolated PSI and P450 membrane complexes using ferredoxin as an electron carrier. The turnover rate of the P450 in the light-driven system was 413 min(-1) compared to 228 min(-1) in the native CPR-catalyzed system. The use of light as a substitute for costly NADPH offers a new avenue for P450-mediated synthesis of complex bioactive natural products using in vitro synthetic biology approaches.
AB - Plants are light-driven "green" factories able to synthesize more than 200,000 different bioactive natural products, many of which are high-value products used as drugs (e.g., artemisinin, taxol, and thapsigargin). In the formation of natural products, cytochrome P450 (P450) monooxygenases play a key role in catalyzing regio- and stereospecific hydroxylations that are often difficult to achieve using the approaches of chemical synthesis. P450-catalyzed monooxygenations are dependent on electron donation typically from NADPH catalyzed by NADPH-cytochrome P450 oxidoreductase (CPR). The consumption of the costly cofactor NADPH constitutes an economical obstacle for biotechnological in vitro applications of P450s. This bottleneck has been overcome by the design of an in vitro system able to carry out light-driven P450 hydroxylations using photosystem I (PSI) for light harvesting and generation of reducing equivalents necessary to drive the P450 catalytic cycle. The in vitro system is based on the use of isolated PSI and P450 membrane complexes using ferredoxin as an electron carrier. The turnover rate of the P450 in the light-driven system was 413 min(-1) compared to 228 min(-1) in the native CPR-catalyzed system. The use of light as a substitute for costly NADPH offers a new avenue for P450-mediated synthesis of complex bioactive natural products using in vitro synthetic biology approaches.
U2 - 10.1021/cb100393j
DO - 10.1021/cb100393j
M3 - Letter
C2 - 21323388
VL - 6
SP - 533
EP - 539
JO - A C S Chemical Biology
JF - A C S Chemical Biology
SN - 1554-8929
IS - 6
ER -
ID: 33894592