کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1257728 971577 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Pathway engineering by designed divergent evolution
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی (عمومی)
پیش نمایش صفحه اول مقاله
Pathway engineering by designed divergent evolution
چکیده انگلیسی

Designed divergent evolution is a proposed protein engineering methodology to redesign enzyme function. The methodology was developed on the basis of the theories of divergent molecular evolution: (i) enzymes with more active and specialized functions have evolved from ones with promiscuous functions; (ii) this process is driven by small numbers of amino acid substitutions (plasticity); and (iii) the effects of double or multiple mutations are often additive (quasi-additive assumption). Thus, in many cases the impact of multiple mutations can be calculated by first determining the effects of a mutation at a single position and subsequently summing these effects using the quasi-additive assumption. In this way, the shape of the fitness landscape of a particular enzyme function can be estimated. The combinations of mutations predicted to yield global optima for desired functions can then be selected and introduced into the enzymes. The methodology has been demonstrated to be very powerful to redesign enzyme function. The use of multiple redesigned enzymes in novel or reconstructed metabolic pathways will enable the production of natural and unnatural products that will find use as pharmaceuticals, agrochemicals and many other applications.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Current Opinion in Chemical Biology - Volume 11, Issue 2, April 2007, Pages 233–239
نویسندگان
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