Harnessing yeast subcellular compartments for the production of plant terpenoids
Harnessing yeast subcellular compartments for the production of plant terpenoids
复制标题
DOI：
10.1016/j.ymben.2011.05.001
复制
发表时间：
2011-09-01
影响因子：
8.4
通讯作者：
Vainstein, Alexander
中科院分区：
文献类型：
--
作者：
Farhi, Moran;Marhevka, Elena;Vainstein, Alexander
生物学和商业上重要的萜类化合物是代谢工程的目标的天然产物的一个大的和多样的类别。然而，在代谢工程的背景下，否则充分记录的代谢酶复合物的空间亚细胞排列已在很大程度上被忽视。为了提高酵母中植物倍半萜的产量，我们增强了甲羟戊酸途径中法呢基二磷酸（EDP）积累的通量，并评估了利用线粒体作为细胞质替代品进行代谢工程的可能性。总之，我们在与截短的和去调节的HMG 1、靶向寡核苷酸的异源EDP合酶和靶向寡核苷酸的倍半萜合酶（即朱栾倍半萜或紫穗槐二烯合酶）共工程化的酵母中分别实现了朱栾倍半萜和紫穗槐二烯的生产的8倍和20倍的改善。利用不同的亚细胞区室的前景为代谢工程的途径，导致有价值的天然化合物开辟了新的和有趣的可能性。(C)2011 Elsevier Inc. All rights reserved.
The biologically and commercially important terpenoids are a large and diverse class of natural products that are targets of metabolic engineering. However, in the context of metabolic engineering, the otherwise well-documented spatial subcellular arrangement of metabolic enzyme complexes has been largely overlooked. To boost production of plant sesquiterpenes in yeast, we enhanced flux in the mevalonic acid pathway toward farnesyl diphosphate (EDP) accumulation, and evaluated the possibility of harnessing the mitochondria as an alternative to the cytosol for metabolic engineering. Overall, we achieved 8- and 20-fold improvement in the production of valencene and amorphadiene, respectively, in yeast co-engineered with a truncated and deregulated HMG1, mitochondrion-targeted heterologous EDP synthase and a mitochondrion-targeted sesquiterpene synthase, i.e. valencene or amorphadiene synthase. The prospect of harnessing different subcellular compartments opens new and intriguing possibilities for the metabolic engineering of pathways leading to valuable natural compounds. (C) 2011 Elsevier Inc. All rights reserved.