초록
<P>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.</P><P><B>Graphic Abstract</B><BR><IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/asbcd6/2018/asbcd6.2018.7.issue-1/acssynbio.7b00269/production/images/medium/sb-2017-00269s_0009.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/sb7b00269'>ACS Electronic Supporting Info</A></P>