Engineering and application of P450 monooxygenases in pharmaceutical and metabolite synthesis

被引:43
作者
Caswell, Jill M. [1 ]
O'Neill, Maeve [1 ]
Taylor, Steve J. C. [1 ]
Moody, Thomas S. [1 ]
机构
[1] Almac, Dept Biocatalysis & Isotope Chem, Craigavon BT63 5QD, North Ireland
关键词
CYTOCHROME-P450; ENZYMES; ACTIVE-SITE; ULTRASOUND; BACTERIAL; BM3; DEALKYLATION; EVOLUTION; OXIDATION; LIBRARY; REGIO;
D O I
10.1016/j.cbpa.2013.01.028
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cytochrome P450 monoxygenase (P450s or CYPs) allow access to drug metabolites, necessary for approval of new therapeutics in one step, with increased success being demonstrated using bacterial and fungal P450s. Moreover, 12 of the 13 products of the human metabolism of verapamil can be accessed through engineered and chimeric bacterial P450s. These P450s are also used in the synthesis of pharmaceuticals themselves, including the semi-synthetic production of artemisinin in an engineered cell. The integration of new technologies including ultrasound and polyfluorinated hydrocarbon solvents offers an attractive means by the true synthetic potential of ubiquitous P450s can be fully realised.
引用
收藏
页码:271 / 275
页数:5
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