Synthesizing Configurable Biochemical Implementation of Linear Systems from Their Transfer Function Specifications

PLoS One. 2015 Sep 9;10(9):e0137442. doi: 10.1371/journal.pone.0137442. eCollection 2015.

Abstract

The ability to engineer synthetic systems in the biochemical context is constantly being improved and has a profound societal impact. Linear system design is one of the most pervasive methods applied in control tasks, and its biochemical realization has been proposed by Oishi and Klavins and advanced further in recent years. However, several technical issues remain unsolved. Specifically, the design process is not fully automated from specification at the transfer function level, systems once designed often lack dynamic adaptivity to environmental changes, matching rate constants of reactions is not always possible, and implementation may be approximative and greatly deviate from the specifications. Building upon the work of Oishi and Klavins, this paper overcomes these issues by introducing a design flow that transforms a transfer-function specification of a linear system into a set of chemical reactions, whose input-output response precisely conforms to the specification. This system is implementable using the DNA strand displacement technique. The underlying configurability is embedded into primitive components and template modules, and thus the entire system is adaptive. Simulation of DNA strand displacement implementation confirmed the feasibility and superiority of the proposed synthesis flow.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Computer Simulation
  • DNA / chemistry*
  • DNA / metabolism
  • Models, Theoretical*
  • Synthetic Biology / methods*

Substances

  • DNA

Grants and funding

The Ministry of Science and Technology, Taiwan, provided support in the form of salaries for authors Tai-Yin Chiu, Hui-Ju Chiang, Ruei-Yang Huang, and Jie-Hong R. Jiang, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the “author contributions” section.