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@Article{ garcia2019,
abstract = {Diversity of cellular metabolism can be harnessed to
produce a large space of molecules. However, development of
optimal strains with high product titers, rates, and yields
required for industrial production is laborious and
expensive. To accelerate the strain engineering process, we
have recently introduced a modular cell design concept that
enables rapid generation of optimal production strains by
systematically assembling a modular cell with an
exchangeable production module(s) to produce target
molecules efficiently. In this study, we formulated the
modular cell design concept as a general multiobjective
optimization problem with flexible design objectives
derived from mass balance. We developed algorithms and an
associated software package, named ModCell2, to implement
the design. We demonstrated that ModCell2 can
systematically identify genetic modifications to design
modular cells that can couple with a variety of production
modules and exhibit a minimal tradeoff among modularity,
performance, and robustness. Analysis of the modular cell
designs revealed both intuitive and complex metabolic
architectures enabling modular production of these
molecules. We envision ModCell2 provides a powerful tool to
guide modular cell engineering and sheds light on modular
design principles of biological systems.},
author = {Garcia, Sergio and Trinh, Cong T},
doi = {10.1016/j.ymben.2018.09.003},
issn = {10967184},
journal = {Metabolic Engineering},
keywords = {Modular cell,Modular cell engineering,Modular
design,Modularity,Multiobjective evolutionary
algorithms,Multiobjective optimization,Production modules},
title = {{Multiobjective strain design: A framework for modular
cell engineering}},
volume = {51},
year = {2019}
}
@Article{ garcia2019b,
title = "Modular design: Implementing proven engineering principles
in biotechnology",
journal = "Biotechnology Advances",
year = "2019",
issn = "0734-9750",
doi = "https://doi.org/10.1016/j.biotechadv.2019.06.002",
url = "http://www.sciencedirect.com/science/article/pii/S0734975019300928",
author = "Sergio Garcia and Cong T. Trinh",
keywords = "Modular design, Modularity, Modular cell, Modular cell
engineering, ModCell, Systems biology, Metabolic
engineering, Synthetic biology, Robustness, Evolvability,
Networks, Pareto optimality, Industrialization of biology,
Microbial biocatalysis",
abstract = "Modular design is at the foundation of contemporary
engineering, enabling rapid, efficient, and reproducible
construction and maintenance of complex systems across
applications. Remarkably, modularity has recently been
discovered as a governing principle in natural biological
systems from genes to proteins to complex networks within a
cell and organism communities. The convergent knowledge of
natural and engineered modular systems provides a key to
drive modern biotechnology to address emergent challenges
associated with health, food, energy, and the environment.
Here, we first present the theory and application of
modular design in traditional engineering fields. We then
discuss the significance and impact of modular
architectures on systems biology and biotechnology. Next,
we focus on the very recent theoretical and experimental
advances in modular cell engineering that seeks to enable
rapid and systematic development of microbial catalysts
capable of efficiently synthesizing a large space of useful
chemicals. We conclude with an outlook towards theoretical
and practical opportunities for a more systematic and
effective application of modular cell engineering in
biotechnology."
}
@Article{ garcia2019c,
author = {Garcia, Sergio and Trinh, Cong T.},
title = {Comparison of Multi-Objective Evolutionary Algorithms to
Solve the Modular Cell Design Problem for Novel
Biocatalysis},
journal = {Processes},
volume = {7},
year = {2019},
number = {6},
article-number= {361},
url = {https://www.mdpi.com/2227-9717/7/6/361},
issn = {2227-9717},
abstract = {A large space of chemicals with broad industrial and
consumer applications could be synthesized by engineered
microbial biocatalysts. However, the current strain
optimization process is prohibitively laborious and costly
to produce one target chemical and often requires new
engineering efforts to produce new molecules. To tackle
this challenge, modular cell design based on a chassis
strain that can be combined with different product
synthesis pathway modules has recently been proposed. This
approach seeks to minimize unexpected failure and avoid
task repetition, leading to a more robust and faster strain
engineering process. In our previous study, we
mathematically formulated the modular cell design problem
based on the multi-objective optimization framework. In
this study, we evaluated a library of state-of-the-art
multi-objective evolutionary algorithms (MOEAs) to identify
the most effective method to solve the modular cell design
problem. Using the best MOEA, we found better solutions for
modular cells compatible with many product synthesis
modules. Furthermore, the best performing algorithm could
provide better and more diverse design options that might
help increase the likelihood of successful experimental
implementation. We identified key parameter configurations
to overcome the difficulty associated with multi-objective
optimization problems with many competing design
objectives. Interestingly, we found that MOEA performance
with a real application problem, e.g., the modular strain
design problem, does not always correlate with artificial
benchmarks. Overall, MOEAs provide powerful tools to solve
the modular cell design problem for novel biocatalysis.},
doi = {10.3390/pr7060361}
}