Synthetic biology—putting engineering into biology

Synthetic biology is interpreted as the engineering-driven building of increasingly complex biological entities for novel applications. Encouraged by progress in the design of artificial gene networks, de novo DNA synthesis and protein engineering, we review the case for this emerging discipline. Key aspects of an engineering approach are purpose-orientation, deep insight into the underlying scientific principles, a hierarchy of abstraction including suitable interfaces between and within the levels of the hierarchy, standardization and the separation of design and fabrication. Synthetic biology investigates possibilities to implement these requirements into the process of engineering biological systems. This is illustrated on the DNA level by the implementation of engineering-inspired artificial operations such as toggle switching, oscillating or production of spatial patterns. On the protein level, the functionally self-contained domain structure of a number of proteins suggests possibilities for essentially Lego-like recombination which can be exploited for reprogramming DNA binding domain specificities or signaling pathways. Alternatively, computational design emerges to rationally reprogram enzyme function. Finally, the increasing facility of de novo DNA synthesis—synthetic biology’s system fabrication process—supplies the possibility to implement novel designs for ever more complex systems. Some of these elements have merged to realize the first tangible synthetic biology applications in the area of manufacturing of pharmaceutical compounds.

Computational enzyme design for industrially relevant reactions

Cognition of life from the perspective of synthetic biology centers on the design, construction, and characterization of novel biological systems using engineering design principles. Most catalytic functions in living organisms are achieved by enzymes, which serve as key components in synthetic biology. While the amino acid sequence makes up the primary structure of the protein, the chemical/biological properties of the protein are dependent on the three-dimensional or tertiary structure. In the nascent field of synthetic biology, researchers are striving to engineer novel biological functionality based on the structures. The development of computational enzyme design algorithms can provide large amounts of prototype molecules for the synthetic biological devices, especially for new catalytic devices, and also provide templates and guidelines for important components of synthetic biology. As the performance of computational algorithms and design strategies continue to improve, protein designers can construct enzymes from scratch and even create highly proficient biocatalysts. This talk provides a brief overview of design principles of proteins and highlights the latest examples of using computational methods to create enzymes for industrially viable applications. References: R. Li et al. Computational redesign of enzymes for regio-and enantioselective hydroamination, Nature chemical biology, 14 (7), 664 (2018). Y. Bu et al. Engineering improved thermostability of the GH11 xylanase from Neocallimastix patriciarum via computational library design, Applied microbiology and biotechnology, 102 (8), 3675-3685 (2018). B. Wu et al. Versatile peptide C-terminal functionalization via a computationally engineered peptide amidase. ACS Catalysis 6 (8), 5405-5414 (2016)

Synthetic Biology Open Language (SBOL) Version 1.1.0

In this BioBricks Foundation Request for Comments (BBF RFC), we specify the Synthetic Biology Open Language (SBOL) Version 1.1.0 to enable the electronic exchange of information describing DNA components used in synthetic biology. We define: 1. the vocabulary, a set of preferred terms and 2. the core data model, a common computational representation

Industrial systems biology and its impact on synthetic biology of yeast cell factories

Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal of developing improved yeast cell factories. (C) 2015 Wiley Periodicals, Inc

Synthetic biology and microdevices : a powerful combination

Recent developments demonstrate that the combination of microbiology with micro-and nanoelectronics is a successful approach to develop new miniaturized sensing devices and other technologies. In the last decade, there has been a shift from the optimization of the abiotic components, for example, the chip, to the improvement of the processing capabilities of cells through genetic engineering. The synthetic biology approach will not only give rise to systems with new functionalities, but will also improve the robustness and speed of their response towards applied signals. To this end, the development of new genetic circuits has to be guided by computational design methods that enable to tune and optimize the circuit response. As the successful design of genetic circuits is highly dependent on the quality and reliability of its composing elements, intense characterization of standard biological parts will be crucial for an efficient rational design process in the development of new genetic circuits. Microengineered devices can thereby offer a new analytical approach for the study of complex biological parts and systems. By summarizing the recent techniques in creating new synthetic circuits and in integrating biology with microdevices, this review aims at emphasizing the power of combining synthetic biology with microfluidics and microelectronics

Synthetic biology tools for environmental protection

Synthetic biology transforms the way we perceive biological systems. Emerging technologies in this field affect many disciplines of science and engineering. Traditionally, synthetic biology approaches were commonly aimed at developing cost-effective microbial cell factories to produce chemicals from renewable sources. Based on this, the immediate beneficial impact of synthetic biology on the environment came from reducing our oil dependency. However, synthetic biology is starting to play a more direct role in environmental protection. Toxic chemicals released by industries and agriculture endanger the environment, disrupting ecosystem balance and biodiversity loss. This review highlights synthetic biology approaches that can help environmental protection by providing remediation systems capable of sensing and responding to specific pollutants. Remediation strategies based on genetically engineered microbes and plants are discussed. Further, an overview of computational approaches that facilitate the design and application of synthetic biology tools in environmental protection is presented

Multi-scale cellular engineering: From molecules to organ-on-a-chip.

Recent technological advances in cellular and molecular engineering have provided new insights into biology and enabled the design, manufacturing, and manipulation of complex living systems. Here, we summarize the state of advances at the molecular, cellular, and multi-cellular levels using experimental and computational tools. The areas of focus include intrinsically disordered proteins, synthetic proteins, spatiotemporally dynamic extracellular matrices, organ-on-a-chip approaches, and computational modeling, which all have tremendous potential for advancing fundamental and translational science. Perspectives on the current limitations and future directions are also described, with the goal of stimulating interest to overcome these hurdles using multi-disciplinary approaches

Applying synthetic biology and computational biology to advance biologics expression platforms

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Computational design of orthogonal microRNAs for synthetic biology

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Upcoming applications of synthetic biology will require access to a wide array of robust genetic components (parts). The logic of a genetic system is encoded with regulatory elements such as pairs of transcription factors:promoters, miRNAs:target sites, or ribozymes:aptamers among others. Due to a relatively simple form and mode of operation of miRNAs, it is possible to design their synthetic variants. Out of all possible miRNA sequences the ones chosen should perform efficiently and should avoid cross-talk with both the host system circuits and within the imported synthetic ones. In this work, a computational method involving a series of heuristics is developed that can be used to design ensembles of such sequences depending on the host transcriptome. As an example, an ensemble of eight such miRNA sequences is produced using this method for use in a human host. Those have then been validated experimentally against the above-mentioned requirements by transfection into HEK 293 cells and flow cytometry measurements of fluorescent markers. The produced sequences are available for use from pENTR vectors of the Gateway cloning system. The required computations were facilitated by a modern cluster computing system—Kaichu—especially developed for this project, but fit for general purpose use and available under an open-source license.EPSR