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科学家已经勾勒出如此一副画面,将来在家自制吗啡会和自制啤酒一样简单。
在家做啤酒,依靠的是酵母将糖转化成酒精的能力。科学家通过将植物DNA通过基因工程嫁接给酵母,让酵母具备一步步将糖转化为吗啡所需系列较复杂化学反应的能力。
其实将微生物用于制药并不是什么新鲜事情,像糖尿病人用的胰岛素,就是通过转基因改造的细菌生产出来的。
吗啡用于镇痛,要通过罂粟获取;若能通过微生物完成这一过程,无疑将更加简单,廉价。
虽然初衷是用于制药,但这无疑将引起关于自制毒品的忧虑:在原则上,只要能够得到这类酵母菌株,具备基本的发酵技巧,就可以像在家自制啤酒一样DIY毒品出来,这无疑是一种很可怕的事情。
立法端正科研行为,管控好这类基因改造的微生物,当未雨绸缪。
http://www.nature.com/nchembio/journal/vaop/ncurrent/full/nchembio.1816.html
An enzyme-coupledbiosensor enables (S)-reticuline production in yeast from glucose
Benzylisoquinolinealkaloids (BIAs) are a diverse family of plant-specialized metabolites thatinclude the pharmaceuticals codeine and morphine and their derivatives.Microbial synthesis of BIAs holds promise as an alternative to traditionalcrop-based manufacturing. Here we demonstrate the production of the key BIAintermediate (S)-reticuline from glucose in Saccharomyces cerevisiae. To aid inthis effort, we developed an enzyme-coupled biosensor for the upstreamintermediate L-3,4-dihydroxyphenylalanine (L-DOPA). Using this sensor, weidentified an active tyrosine hydroxylase and improved its L-DOPA yields by 2.8-foldvia PCR mutagenesis. Coexpression of DOPA decarboxylase enabled what is to ourknowledge the first demonstration of dopamine production from glucose in yeast,with a 7.4-fold improvement in titer obtained for our best mutant enzyme. Weextended this pathway to fully reconstitute the seven-enzyme pathway fromL-tyrosine to (S)-reticuline. Future work to improve titers and connect thesesteps with downstream pathway branches, already demonstrated in S. cerevisiae,will enable low-cost production of many high-value BIAs.
群晓科苑
qbioscience.com
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