scholarly journals Multiobjective Strain Design: A Framework for Modular Cell Engineering

2018 ◽  
Author(s):  
Sergio Garcia ◽  
Cong T. Trinh

ABSTRACTDiversity 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 action. 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.

2017 ◽  
Author(s):  
Brandon Wilbanks ◽  
Donovan S. Layton ◽  
Sergio Garcia ◽  
Cong T. Trinh

ABSTRACTWhen 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 and exchangeable production modules in a plug-and-play fashion. In this study, we experimentally validated some designed properties of MODCELL by demonstrating: 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.


Processes ◽  
2019 ◽  
Vol 7 (6) ◽  
pp. 361 ◽  
Author(s):  
Sergio Garcia ◽  
Cong T. Trinh

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.


2019 ◽  
Author(s):  
Sergio Garcia ◽  
Cong Trinh

AbstractA 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 been recently proposed. This approach seeks to minimize unexpected failure and avoid task repetition, leading to a more robust and faster strain engineering process. The modular cell design problem was mathematically formulated using a multi-objective optimization framework.[1] In this study, we evaluated a library of the 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.


Author(s):  
Israel Aguilera Navarrete ◽  
Alejandro A. Lozano Guzmán

According to INEGI (National Institute for Statistics and Geography), in 2004 there were around 730,000 people in Mexico with the need of some kind of mechanical aid to regain ability to walk. Support equipment for regaining the ability to walk normally is manufactured outside of Mexico. This equipment is complex and very expensive. In this work, the design of a walking ability rehabilitation aid is presented. This work is carried out applying the modular design concept. This ensures that all client needs are fulfilled by the resultant product, and that these needs are measurable and controllable. Basic idea behind this design is supporting part of patient’s weight and that of an exoskeleton on a mechanical device. Basic kinematics and dynamic calculation are presented, as well as simulations results. This information shows the feasibility of building and operating this rehabilitation walking aid.


2014 ◽  
Vol 955-959 ◽  
pp. 3323-3330
Author(s):  
Zhi Wei Xiao ◽  
Jia He ◽  
Nan Qi ◽  
Jia Peng Wen ◽  
Xiu Bo Chen ◽  
...  

With biofilm reactor and continuous membrane filtration as the core, this paper proposes to establish biochemical module and membrane processing module, which can from the biofilm - membrane filtration process. In the part of biochemical module, diverse processing function can be realized by adjusting the operation conditions of the pumps and fans. Meanwhile, the number and operation condition of biochemical module could be changed flexibly according to the actual processing needs. Thereby, the standardization and generalization of biochemical module can be achieved. And in the part of membrane processing module, the processing capacity can also be expanded through frequency converting control and increasing the number of membrane module. An engineering project of decentralized sewage reuse is built, and the outlet water quality can reach the expected standard, which suggests that the modular design concept has good feasibility.


2019 ◽  
Vol 39 (5) ◽  
pp. 630-657 ◽  
Author(s):  
Risto Rajala ◽  
Saara A. Brax ◽  
Ari Virtanen ◽  
Anna Salonen

Purpose The purpose of this paper is to identify integrated solutions business as the first generation of servitized offerings and modular solution offerings as the second development phase in servitization of original equipment manufacturers. This study examines how the servitized manufacturer, Kone, moves from integrated solutions to modular solutions business and develops the requisite capabilities to design, produce and implement modular solution offerings. Design/methodology/approach The paper reports a longitudinal case study of a provider of integrated solutions installed in buildings. During the ten years studied, the manufacturer implemented a strategic initiative to modularize its integrated solutions offering. Findings The firm’s transition to modular solutions progressed through three major capability development phases: solutions based on ad hoc integration, smart solutions based on modular design and through-chain modularity. The modular structure aims at fostering the efficiency of the solution offering and the associated production system. Research limitations/implications Leveraging the benefits of modularity calls for an aligned combination of strategic, operational and technical capabilities contributing to the integration of resources in a modular production system for the solution providers’ competitive performance. Practical implications The study reports how a solution provider can develop the operational capabilities to integrate the core and peripheral components into the solution, and orchestrate the modular production system. Originality/value This study is a rare longitudinal analysis of how a manufacturer builds a modular offering, the solution platform and the required competitive capabilities to provide the solution.


2011 ◽  
Vol 55-57 ◽  
pp. 614-617
Author(s):  
Dong Yun Luo ◽  
You Mu Zhang

The network communication system is presented for controller of AT91SAM9261 architecture which is based on ARM926EJ-S core, modular design concept is given by the each har­d­ware related module and driver design. High processing speed of the system on the basis of this system can be extended .


2013 ◽  
Vol 401-403 ◽  
pp. 207-209
Author(s):  
Shu Lei Wu ◽  
Li Zhen Zhang ◽  
Yang Zhao

With the rise of mass customization production, the advantages of modular design are highlighted. Through the selection and combination of modules, different products can be made. It can help to meet the various market demands for the product design. The modular design concept in the small aquatic cutting machine, can enhance product innovation, shorten the design cycle and improve the degree of customization.


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