Turn­ing up the heat on enzyme design

To give them great­er range, and poten­tially more applic­a­tions, a team of Yale engin­eers led by assist­ant pro­fess­or of chem­ic­al and envir­on­ment­al engin­eer­ing Corey Wilson has developed a meth­od for design­ing tem­per­at­ure adapt­ive enzymes. The innov­a­tion, believed to be the first of its kind, com­ple­ments pre­vi­ous exper­i­ments focused solely on enzyme struc­ture and flex­ib­il­ity, the sequence of the enzyme’s amino acid build­ing blocks, or how the enzyme util­izes energy. Using Wilson’s meth­od, enzymes can be designed to func­tion at spe­cif­ic tem­per­at­ure ranges. ​“We can now make enzymes that can be used at high­er or lower tem­per­at­ures and under harsh con­di­tions,” says Wilson. ​“You might say to me, ​‘Look, I need to cata­lyze this indus­tri­al reac­tion at a hun­dred degrees, I need a sys­tem to do this cata­lys­is.’ Now we can cre­ate an enzyme to do that.” For example, an enzyme could be mod­i­fied for use in bio­fuel pro­duc­tion, where the high tem­per­at­ure (approach­ing 200 degrees Celsi­us) pre­treat­ments would cause the cur­rently avail­able enzymes to lose their struc­ture. Altern­at­ively, for patients whose body tem­per­at­ures have been arti­fi­cially lowered dur­ing car­di­op­ul­mon­ary bypass sur­gery, an enzyme could be designed to more effi­ciently return thinned blood to its nor­mal state, thereby improv­ing safety. In addi­tion to such applic­a­tions, tem­per­at­ure adapt­ive enzyme design has also enabled the team to accur­ately identi­fy the ther­mo­dy­nam­ic lim­its of pro­tein func­tion. Giv­en merely a fin­ger­print of a pro­tein or the hint of a pro­tein, the new meth­od could the­or­et­ic­ally pre­dict the envir­on­ments in which an organ­ism might live. ​“You can extra­pol­ate that to any­place,” Wilson says. ​“You can go off the plan­et into the uni­verse and you can say here are the con­di­tions that would sup­port this kind of enzyme. It can be used as a pre­dict­ive tool to determ­ine the ther­mo­dy­nam­ic lim­its of life.” Oth­er mem­bers of Wilson’s team include Stan­ley C. How­ell, Krishna Kis­hore Inam­pudi, and Doyle P. Bean, all of Yale. Their research was recently pub­lished in the journ­al Struc­ture. Source: School of Engin­eer­ing & Applied Sci­ence, Yale University