Programmable chemical reaction networks: emulating regulatory functions in living cells using a bottom-up approach

Abstract

Living cells are able to produce a wide variety of biological responses when subjected to biochemical stimuli. It has become apparent that these biological responses are regulated by complex chemical reaction networks (CRNs). Unravelling the function of these circuits is a key topic of both systems biology and synthetic biology. Recent progress at the interface of chemistry and biology together with the realisation that current experimental tools are insufficient to quantitatively understand the molecular logic of pathways inside living cells has triggered renewed interest in the bottom-up development of CRNs. This builds upon earlier work of physical chemists who extensively studied inorganic CRNs and showed how a system of chemical reactions can give rise to complex spatiotemporal responses such as oscillations and pattern formation. Using purified biochemical components, in vitro synthetic biologists have started to engineer simplified model systems with the goal of mimicking biological responses of intracellular circuits. Emulation and reconstruction of system-level properties of intracellular networks using simplified circuits are able to reveal key design principles and molecular programs that underlie the biological function of interest. In this Tutorial Review, we present an accessible overview of this emerging field starting with key studies on inorganic CRNs followed by a discussion of recent work involving purified biochemical components. Finally, we review recent work showing the versatility of programmable biochemical reaction networks (BRNs) in analytical and diagnostic applications.

Computer‐aided biochemical programming of synthetic microreactors as diagnostic devices

“…Moore's law), automated design frameworks are required to build biochemical control circuits de novo (Chandran et al , ; Chiang et al , ). Although progress in design automation of synthetic gene circuits has been made (Marchisio & Stelling, ; Van Roekel et al , ; Delépine et al , ; Nielsen et al , ), to date no clear engineering principles or methodologies exist to design cell‐free synthetic reaction‐based logic systems according to specifications, while using a variety of reactive biochemical species of different nature. Furthermore, in the same way natural cells rely on membrane compartmentalization and localization of metabolons to support complex operations to be performed, microarchitectures are required within which biochemical circuitry can be insulated to allow spatial segregation, parallelization of processes, and multiplexed signal processing (Elani et al , ).…”

Microfluidics for Biosynthesizing: from Droplets and Vesicles to Artificial Cells

“…Numerous works have reported the utilization of artificial cells as platforms for chemical reactions, control release, drug delivery, and biosensing applications The artificial‐cell‐based bioreactors can be operated in high efficiency and high throughput for conducting chemical reactions. Different from the natural‐cell‐based bioreactor, the well‐defined artificial cells can allow the chemical reactions being executed in specific pathways with the maximum atomic utilization.…”

Unconventional Nonlinear Input–Output Response in a Luminescent Molecular Switch by Inner Filtering Effects

“…[17] Acetonitrile Merck Uvasol was employed as the solvent in all the experiments. Triflic acid (CF 3 SO 3 H) and tributylamine (nBu 3 N) were purchased from Fluka and used without further purification.…”

“…[15] Nonlinear information processing has been demonstrated using biomolecular reactions (in most cases on enzyme-based systems), and logic operations with filtering functions that reduce noise have been obtained. [14,16] As far as synthetic systems are concerned, while the responses shown in Figure1b-d can be obtained with catalytic reaction networks, [17] their implementation with bistable comNonlinear input-output relations are at the basis of the regulation of biochemical processes in living organisms and are important for the development of digital logic circuits based on molecules. In this article we show that al inear change of ac hemical inputc an be translated into an exponentialc hange of al uminescenceo utput in as imple fluorescent acid-base switch based on 8-methoxyquinoline.S uch unconventional behavior arises from the fact that part of the light emitted by the switch in its basic form is reabsorbed by the acid form, and is made possible by the particular spectroscopic properties of the two forms.S ystems of this kind could act as noise filters in analog-to-digital conversion,a nd as control elements to increase the functional complexity of artificial molecular devices.…”