Symmetry breaking meets multisite modification

Multisite modification is a basic way of conferring functionality to proteins and a key component of post-translational modification networks. Additional interest in multisite modification stems from its capability of acting as complex information processors. In this paper, we connect two seemingly disparate themes: symmetry and multisite modification. We examine different classes of random modification networks of substrates involving separate or common enzymes. We demonstrate that under different instances of symmetry of the modification network (invoked explicitly or implicitly and discussed in the literature), the biochemistry of multisite modification can lead to the symmetry being broken. This is shown computationally and consolidated analytically, revealing parameter regions where this can (and in fact does) happen, and characteristics of the symmetry-broken state. We discuss the relevance of these results in situations where exact symmetry is not present. Overall, through our study we show how symmetry breaking (i) can confer new capabilities to protein networks, including concentration robustness of different combinations of species (in conjunction with multiple steady states); (ii) could have been the basis for ordering of multisite modification, which is widely observed in cells; (iii) can significantly impact information processing in multisite modification and in cell signalling networks/pathways where multisite modification is present; and (iv) can be a fruitful new angle for engineering in synthetic biology and chemistry. All in all, the emerging conceptual synthesis provides a new vantage point for the elucidation and the engineering of molecular systems at the junction of chemical and biological systems.

Synthetic biology is built on genetic engineering and principles of design engineering, which provides control over the biological functions of interest. This chapter explores the uses, processes, and applications of genetic engineering in synthetic biology. The chapter provides a brief history and course of development of the field of synthetic biology and genetic engineering and their unbreakable association. Next, the chapter delves into materials and methods and the applications of synthetic biology. This includes discussing the generally used components of genetic engineering to design new functions into organisms and even the general steps that are part of any synthetic biology experiment. Lastly, the chapter also explains the use of the materials and methodology discussed in solving a specific problem related to amodel mentioned in the paper titled"Development of Integrase-mediated differentiation circuits to improve evolutionary stability in E. coli." It explains how by using genetic engineering a synthetic biology-related problem was solved efficiently.

Paving the way for synthetic biology‐based bioremediation in Europe

Bistability, and more generally multistability, is a key system dynamics feature enabling decision-making and memory in cells. Deciphering the molecular determinants of multistability is thus crucial for a better understanding of cellular pathways and their (re)engineering in synthetic biology. Here, we show that a key motif found predominantly in eukaryotic signalling systems, namely a futile signalling cycle, can display bistability when featuring a two-state kinase. We provide necessary and sufficient mathematical conditions on the kinetic parameters of this motif that guarantee the existence of multiple steady states. These conditions foster the intuition that bistability arises as a consequence of competition between the two states of the kinase. Extending from this result, we find that increasing the number of kinase states linearly translates into an increase in the number of steady states in the system. These findings reveal, to our knowledge, a new mechanism for the generation of bistability and multistability in cellular signalling systems. Further the futile cycle featuring a two-state kinase is among the smallest bistable signalling motifs. We show that multi-state kinases and the described competition-based motif are part of several natural signalling systems and thereby could enable them to implement complex information processing through multistability. These results indicate that multi-state kinases in signalling systems are readily exploited by natural evolution and could equally be used by synthetic approaches for the generation of multistable information processing systems at the cellular level.

BiotecVisions 2012, April

Advances in our scientific understanding and technological power in recent decades have dramatically amplified our capacity to intentionally manipulate complex ecological and biological systems. An implication of this is that biological and ecological problems are increasingly understood and approached from an engineering perspective. In environmental contexts, this is exemplified in the pursuits of geoengineering, designer ecosystems, and conservation cloning. In human health contexts, it is exemplified in the development of synthetic biology, bionanotechnology, and human enhancement technologies. Designer Biology: The Ethics of Intensively Engineering Biological and Ecological Systems consists of thirteen chapters (twelve of them original to the collection) that address the ethical issues raised by technological intervention and design across a broad range of biological and ecological systems. Among the technologies addressed are geoengineering, human enhancement, sex selection, genetic modification, and synthetic biology. This collection advances and enriches our understanding of the ethical issues raised by these technologies and identifies general lessons about the ethics of engineering complex biological and ecological systems that can be applied as new technologies and practices emerge. The insights that emerge will be especially valuable to students and scholars of environmental ethics, bioethics, or technology ethics.

Synthetic biology is an interdisciplinary field that combines engineering principles to design and construct new biological components, devices, and systems for understanding and reprogramming biological functions. This field aims to create novel biological entities with specific functions or solutions to particular problems through precise manipulation of biomolecules and cells. Bladder cancer is a type of cancer that originates in the tissues of the urinary bladder and primarily affects the urothelial cells lining the bladder wall. Synthetic biology technology, while relatively new for the treatment of bladder cancer, has promising potential for providing innovative solutions for the detection, treatment, and management of bladder cancer. This article reviews the latest research progress in the field of synthetic biology applied to bladder cancer. This research focuses on the application of gene editing technologies such as CRISPR–CRISPR-associated protein 9 to precisely modify the genome of bladder cancer cells to inhibit their growth and proliferation. Additionally, it introduces methods for enhancing antitumor immune responses through the modification of immune cells, such as chimeric antigen receptor-T-cell therapy. Furthermore, this article explores the potential of the use of genetically engineered bacteria as an emerging treatment option for bladder cancer. Despite challenges such as targeting specificity, safety, and cost, synthetic biology technologies provide new perspectives and strategies for the treatment of bladder cancer. With continuous advancements in technology and strengthened interdisciplinary collaboration, the application of synthetic biology in bladder cancer treatment holds great promise, potentially offering patients new treatment options and hope.

Synthetic biology stretching the realms of possibility in wine yeast research

BackgroundMany difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects.ResultsHere I propose a novel framework that brings together evolutionary theory and current systems biology approaches in order to quantify small effects of mutations and their epistatic interactions in silico. Central to this approach is the definition of fitness correlates that can be computed in some current systems biology models employing the rigorous algorithms that are at the core of much work in computational systems biology. The framework exploits synergies between the realism of such models and the need to understand real systems in evolutionary theory. This framework can address many longstanding topics in evolutionary biology by defining various 'levels' of the adaptive landscape. Addressed topics include the distribution of mutational effects on fitness, as well as the nature of advantageous mutations, epistasis and robustness. Combining corresponding parameter estimates with population genetics models raises the possibility of testing evolutionary hypotheses at a new level of realism.ConclusionEvoSysBio is expected to lead to a more detailed understanding of the fundamental principles of life by combining knowledge about well-known biological systems from several disciplines. This will benefit both evolutionary theory and current systems biology. Understanding robustness by analysing distributions of mutational effects and epistasis is pivotal for drug design, cancer research, responsible genetic engineering in synthetic biology and many other practical applications.

SyPro Poplar: Improving Poplar Biomass Production under Abiotic Stress Conditions: an Integrated Omics, Bioinformatics, Synthetic Biology and Genetic Engineering Approach In the SyPro Poplar project, we aimed to integrate omics, bioinformatics, synthetic biology, and genetic engineering approaches to develop transgenic poplar trees with sustained photosynthetic activity and increased biomass production under individual and the simultaneous occurrence of water deficit, increased soil salinity, and elevated temperatures. Specifically, we intended to (i) study the functions of selected stress-responsive genes at tissue and cell type-specific levels, (ii) discover novel motifs and construct stress-responsive synthetic promoters, and (iii) use these promoters to drive the expression of genes shown to confer abiotic stress tolerance in a variety of crops and develop abiotic stress-tolerant poplars in a coordinated fashion.

Hemoglobin is an essential protein to the human body as it transports oxygen to organs and tissues through the bloodstream (Looker et al., 1992). In recent years, there has been an increasing concern regarding the global supply of this vital protein, as blood availability cannot currently meet the high demands in many developing countries. There are, in addition, several risks associated with conventional blood transfusions such as the presence of blood-borne viruses like HIV and Hepatitis. These risks along with some limitations are presented in Figure 1 (Kim and Greenburg, 2013; Martínez et al., 2015). As an alternative, producing hemoglobin recombinantly will eliminate the obstacles, since hemoglobin-based oxygen carriers are pathogen-free, have a longer shelf-life, are universally compatible and the supply can be adjusted to meet the demands (Chakane, 2017). A stable, safe, and most importantly affordable production, will lead to high availability of blood to the world population, and hence reduce global inequality, which is a focus point of the World Health Organization for the millennium (WHO, 2018). Synthetic biology and metabolic engineering have created a unique opportunity to construct promising candidates for hemoglobin production (Liu et al., 2014; Martínez et al., 2016). This review sets out to describe the recent advances in recombinant hemoglobin production, the societal and the economic impact along with the challenges that researchers will face in the coming years, such as low productivity, degradation, and difficulties in scale-up. The challenges are diverse and complex but with the powerful tools provided by synthetic biology and metabolic engineering, they are no longer insurmountable. An efficient production of cell-free recombinant hemoglobin poses tremendous challenges while having even greater potential, therefore some possible future directions are suggested in this review.

Metabolic engineering, a core pillar of synthetic biology, enables the precise reprogramming of cellular metabolism for efficient production of valuable compounds. This review outlines recent advances in genome editing, pathway construction, and dynamic regulation strategies that underpin modern metabolic engineering. Emerging tools such as CRISPR-derived editors, machine learning-guided design, and automated high-throughput workflows have accelerated the design–build–test–learn cycle and enabled predictive strain optimization. Applications span microbial cell factories, mammalian and plant hosts, cell-free biosynthesis systems, synthetic consortia, and non-traditional chassis such as photosynthetic microbes, extremophiles, and filamentous fungi. These engineered systems have facilitated the biosynthesis of fuels, pharmaceuticals, specialty chemicals, and nutraceuticals, often under environmentally sustainable conditions. Challenges remain in scaling processes, overcoming metabolic bottlenecks, and ensuring biosafety in complex systems. Nevertheless, the integration of systems biology, artificial intelligence, and synthetic design is ushering in a new era of intelligent and modular biomanufacturing. Continued innovation in chassis development, global metabolic rewiring, and closed-loop automation will further expand the capabilities and impact of metabolic engineering across biotechnology and industrial applications.

Covering: up to 2013. Although holo-acyl carrier protein synthase, AcpS, a phosphopantetheinyl transferase (PPTase), was characterized in the 1960s, it was not until the publication of the landmark paper by Lambalot et al. in 1996 that PPTases garnered wide-spread attention being classified as a distinct enzyme superfamily. In the past two decades an increasing number of papers have been published on PPTases ranging from identification, characterization, structure determination, mutagenesis, inhibition, and engineering in synthetic biology. In this review, we comprehensively discuss all current knowledge on this class of enzymes that post-translationally install a 4'-phosphopantetheine arm on various carrier proteins.

The imminent role of protein engineering in synthetic biology

3rd congress on applied synthetic biology in Europe (Costa da Caparica, Portugal, February 2016)