Spatial organization of enzymes for metabolic engineering
Spatial organization of enzymes for metabolic engineering
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DOI：
10.1016/j.ymben.2011.09.003
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发表时间：
2012-05-01
影响因子：
8.4
通讯作者：
Dueber, John E.
中科院分区：
文献类型：
--
作者：
Lee, Hanson;DeLoache, William C.;Dueber, John E.
随着由外源酶构建的合成途径变得更加复杂，遇到与宿主生物体的不期望的相互作用的可能性增加，从而降低产物滴度。一个新兴的策略，以解决这个问题是空间组织的途径酶成多蛋白质复合物，其中高浓度的酶和代谢物的局部可能会提高流量和限制有问题的相互作用与细胞环境。使用合成支架的共定位酶提高了多个途径的滴度。虽然缺乏物理扩散屏障，但支架系统可以通过类似于天然存在的微区的机制局部浓缩中间体。一个更直接的划分途径成分的策略是将它们封装在蛋白质壳内。几类壳已经负载外源蛋白并在工业宿主中成功表达。实现蛋白质壳理想途径区室化的一个关键挑战可能是演变孔隙以选择性限制中间扩散。最终，这些工具应该可以增强我们合理设计代谢途径的能力。(C)2011 Elsevier Inc. All rights reserved.
As synthetic pathways built from exogenous enzymes become more complicated, the probability of encountering undesired interactions with host organisms increases, thereby lowering product titer. An emerging strategy to combat this problem is to spatially organize pathway enzymes into multi-protein complexes, where high local concentrations of enzymes and metabolites may enhance flux and limit problematic interactions with the cellular milieu. Co-localizing enzymes using synthetic scaffolds has improved titers for multiple pathways. While lacking physical diffusion barriers, scaffolded systems could concentrate intermediates locally through a mechanism analogous to naturally occurring microdomains. A more direct strategy for compartmentalizing pathway components would be to encapsulate them within protein shells. Several classes of shells have been loaded with exogenous proteins and expressed successfully in industrial hosts. A critical challenge for achieving ideal pathway compartmentalization with protein shells will likely be evolving pores to selectively limit intermediate diffusion. Eventually, these tools should enhance our ability to rationally design metabolic pathways. (C) 2011 Elsevier Inc. All rights reserved.