目前,，一個(gè)由捷克斯洛伐克共和國(guó),，德國(guó)和日本的科學(xué)家組成的科研小組開發(fā)了一種提高酶性能新方法。該方法或能用于化學(xué),，醫(yī)學(xué)和食品工業(yè),。
這項(xiàng)研究結(jié)果發(fā)布在Nature Chemical Biology上。
一些由于人類活動(dòng)而進(jìn)入環(huán)境中的化學(xué)物質(zhì),，對(duì)人類和動(dòng)物健康會(huì)產(chǎn)生嚴(yán)重的消極影響,，往往很多是大自然不能自行降解的。這種改進(jìn)的酶能夠用于有害化學(xué)物質(zhì)的清除,，可以更加高效地移除環(huán)境中的有害化學(xué)物質(zhì),。
這項(xiàng)發(fā)現(xiàn)是基于酶的基因操作，經(jīng)處理的酶能夠高效地促進(jìn)化學(xué)反應(yīng),。研究人員介紹說(shuō),，現(xiàn)在他們能夠使用基因修飾改變酶的性能，使得酶更快地分解環(huán)境中的有害物質(zhì),。
科學(xué)家一直關(guān)注于酶活性位點(diǎn)的修飾,。這種新的方法，能夠通過(guò)一種叫進(jìn)口通道（access tunnels）的修飾連接酶表面的活性位點(diǎn),。
科研人員用這種方法修飾一種能降解劇毒物質(zhì)三氯丙烷(TCP)的酶,，TCP是化學(xué)生產(chǎn)的次級(jí)產(chǎn)物，能夠在土壤和地下水中存在100多年,，會(huì)污染飲用水也是一種致癌源,。蛋白質(zhì)工程人員使用該新方法修飾的酶，其降解TCP的速度比原來(lái)的酶快了32倍,。
此外,，不僅僅是用于降解有害物質(zhì)和環(huán)境保護(hù)，這種方法還可用于更廣泛的領(lǐng)域,，包括生物醫(yī)學(xué),，化學(xué)和食品工業(yè)。（生物谷Bioon.com）
生物谷國(guó)慶專題：新中國(guó)生命科學(xué)60年
生物谷推薦原始出處：
Nature Chemical Biology 5, 727 - 733 (2009)23 August 2009 | doi:10.1038/nchembio.205
Redesigning dehalogenase access tunnels as a strategy for degrading an anthropogenic substrate
Martina Pavlova1,5, Martin Klvana1,5, Zbynek Prokop1, Radka Chaloupkova1, Pavel Banas2, Michal Otyepka2, Rebecca C Wade3, Masataka Tsuda4, Yuji Nagata4 & Jiri Damborsky1
Abstract
Engineering enzymes to degrade anthropogenic compounds efficiently is challenging. We obtained Rhodococcus rhodochrous haloalkane dehalogenase mutants with up to 32-fold higher activity than wild type toward the toxic, recalcitrant anthropogenic compound 1,2,3-trichloropropane (TCP) using a new strategy. We identified key residues in access tunnels connecting the buried active site with bulk solvent by rational design and randomized them by directed evolution. The most active mutant has large aromatic residues at two out of three randomized positions and two positions modified by site-directed mutagenesis. These changes apparently enhance activity with TCP by decreasing accessibility of the active site for water molecules, thereby promoting activated complex formation. Kinetic analyses confirmed that the mutations improved carbon-halogen bond cleavage and shifted the rate-limiting step to the release of products. Engineering access tunnels by combining computer-assisted protein design with directed evolution may be a valuable strategy for refining catalytic properties of enzymes with buried active sites.
1 Loschmidt Laboratories, Institute of Experimental Biology and National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno, Czech Republic.
2 Department of Physical Chemistry and Center for Biomolecules and Complex Molecular Systems, Palacky University, Olomouc, Czech Republic.
3 Molecular and Cellular Modeling Group, EML Research gGmbH, Heidelberg, Germany.
4 Department of Environmental Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan.
5 These authors contributed equally to this work.
