posted on 2017-10-10, 00:00authored byBrandon Wilbanks, Donovan S. Layton, Sergio Garcia, Cong T. Trinh
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.