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A Prototype for Modular Cell Engineering
ACS Synthetic Biology ( IF 4.7 ) Pub Date : 2017-11-22 00:00:00 , DOI: 10.1021/acssynbio.7b00269
Brandon Wilbanks 1 , Donovan S. Layton 1 , Sergio Garcia 1 , Cong T. Trinh 1
Affiliation  

When aiming to produce a target chemical at high yield, titer, and productivity, various combinations of genetic parts available to build the target pathway can generate a large number of strains for characterization. This engineering approach will become increasingly laborious and expensive when seeking to develop desirable strains for optimal production of a large space of biochemicals due to extensive screening. Our recent theoretical development of modular cell (MODCELL) design principles can offer a promising solution for rapid generation of optimal strains by coupling a modular cell with exchangeable production modules in a plug-and-play fashion. In this study, we experimentally validated some design properties of MODCELL by demonstrating the following: (i) a modular (chassis) cell is required to couple with a production module, a heterologous ethanol pathway, as a testbed, (ii) degree of coupling between the modular cell and production modules can be modulated to enhance growth and product synthesis, (iii) a modular cell can be used as a host to select an optimal pyruvate decarboxylase (PDC) of the ethanol production module and to help identify a hypothetical PDC protein, and (iv) adaptive laboratory evolution based on growth selection of the modular cell can enhance growth and product synthesis rates. We envision that the MODCELL design provides a powerful prototype for modular cell engineering to rapidly create optimal strains for synthesis of a large space of biochemicals.

中文翻译:

模块化细胞工程的原型

当旨在以高收率,效价和生产率生产目标化学品时,可用于构建目标途径的遗传部分的各种组合会产生大量用于鉴定的菌株。当由于广泛的筛选而试图开发理想的菌株以最佳地生产大面积的生化试剂时,这种工程方法将变得越来越费力和昂贵。我们最近对模块化单元格(MODCELL)设计原理的理论发展,可以通过以即插即用的方式将模块化单元格与可互换的生产模块耦合在一起,为快速生成最佳菌株提供有希望的解决方案。在本研究中,我们通过演示以下内容,通过实验验证了MODCELL的一些设计属性:(i)需要一个模块化(底盘)电池与生产模块耦合,作为测试平台的异源乙醇途径,(ii)可以调节模块化细胞与生产模块之间的偶联程度,以增强生长和产物合成,(iii)模块化细胞可以用作宿主,以选择最佳的丙酮酸脱羧酶(PDC)的乙醇生产模块,并帮助鉴定假想的PDC蛋白;(iv)基于模块化细胞生长选择的适应性实验室进化可以提高生长和产物合成速率。我们设想MODCELL设计为模块化细胞工程提供了一个强大的原型,可以快速创建用于合成大量生物化学物质的最佳菌株。(iii)模块化细胞可用作宿主,以选择乙醇生产模块的最佳丙酮酸脱羧酶(PDC)并帮助鉴定假想的PDC蛋白;和(iv)基于模块化细胞生长选择的适应性实验室进化可以提高增长速度和产品合成率。我们设想MODCELL设计为模块化细胞工程提供了一个强大的原型,可以快速创建用于合成大量生物化学物质的最佳菌株。(iii)模块化细胞可用作宿主,以选择乙醇生产模块的最佳丙酮酸脱羧酶(PDC)并帮助鉴定假想的PDC蛋白;和(iv)基于模块化细胞生长选择的适应性实验室进化可以提高增长速度和产品合成率。我们设想MODCELL设计为模块化细胞工程提供了一个强大的原型,可以快速创建用于合成大量生物化学物质的最佳菌株。
更新日期:2017-11-22
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