| Light-driven Cytochrome P450 Hydroxylations. | |
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MedLine Citation:
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PMID: 21323388 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Plants are light-driven "green" factories able to synthesize more than 200,000 different bio-active 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 stoichiometric 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<sup>-1</sup> compared to 228 min<sup>-1</sup> 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. |
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Authors:
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Kenneth Jensen; Poul Erik Jensen; Birger Lindberg Møller |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-2-16 |
Journal Detail:
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Title: ACS chemical biology Volume: - ISSN: 1554-8937 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-2-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101282906 Medline TA: ACS Chem Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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