To produce a target chemical at high yields, titers, and productivities, various combinations of available genetic parts for expression system can result in a large number of microbial cell factories generated for characterization. This engineering approach will become increasingly laborious and expensive when seeking to develop optimal strains for 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 modular optimal production strains in a systematic manner using a modular cell and exchangeable production modules. Here, we present validation of the MODCELL design and development of a modular cell engineering prototype. We demonstrate i) a modular (chassis) cell is required to tightly couple with a production module (e.g., alcohols and esters), ii) degree of coupling between the modular cell and production modules can be modulated to enhance product synthesis, iii) a modular cell can be used as a host to select and discover functions of hypothetical proteins, and iv) metabolic pathway evolution based on growth selection could enhance growth and product rates of the weakly coupled cells. We envision that MODCELL provides a powerful platform for rapid development of optimal production strains in a plug-and-play fashion to produce a large space of biochemicals.

MODCELL: A prototype for modular cell engineering

255th National Meeting (2018)

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