A Novel Semi-biosynthetic Route for Artemisinin Production Using Engineered Substrate-Promiscuous P450BM3 [electronic resource].
- Published:
- Berkeley, Calif. : Lawrence Berkeley National Laboratory, 2009.
Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy. - Physical Description:
- 7 : digital, PDF file
- Additional Creators:
- Lawrence Berkeley National Laboratory and United States. Department of Energy. Office of Scientific and Technical Information
Access Online
- Restrictions on Access:
- Free-to-read Unrestricted online access
- Summary:
- Production of fine heterologus pathways in microbial hosts is frequently hindered by insufficient knowledge of the native metabolic pathway and its cognate enzymes; often the pathway is unresolved and enzymes lack detailed characterization. An alternative paradigm to using native pathways is de novo pathway design using well-characterized, substrate-promiscuous enzymes. We demonstrate this concept using P450BM3 from Bacillus megaterium. Using a computer model, we illustrate how key P450BM3 activ site mutations enable binding of non-native substrate amorphadiene, incorporating these mutations into P450BM3 enabled the selective oxidation of amorphadiene arteminsinic-11s,12-epoxide, at titers of 250 mg L"1 in E. coli. We also demonstrate high-yeilding, selective transformations to dihydroartemisinic acid, the immediate precursor to the high value anti-malarial drug artemisinin.
- Report Numbers:
- E 1.99:lbnl-2938e
lbnl-2938e - Other Subject(s):
- Note:
- Published through SciTech Connect.
11/30/2009.
"lbnl-2938e"
American Chemical Society Journal of Chemical Biology 4 4 FT
Fisher, Karl; Baker, David; Keasling, Jay; Renninger, Neil; Dietrich, Jeffrey; Yoshikuni, Yasuo; Woolard, Frank; Ockey, Denise; McPhee, Derek; Chang, Michelle. - Funding Information:
- DE-AC02-05CH11231
View MARC record | catkey: 13809062