scholarly journals RetroPath2.0: a retrosynthesis workflow for metabolic engineers

2017 ◽  
Author(s):  
Baudoin Delépine ◽  
Thomas Duigou ◽  
Pablo Carbonell ◽  
Jean-Loup Faulon
Keyword(s):  
Synthetic Biology ◽  
Open Source ◽  
Computer Aided Design ◽  
Reaction Network ◽  
Ease Of Use ◽  
Chemical Diversity ◽  
Industrial Biotechnology ◽  
List Type ◽  
Enzyme Promiscuity ◽  
Main Challenge

AbstractSynthetic biology applied to industrial biotechnology is transforming the way we produce chemicals. However, despite advances in the scale and scope of metabolic engineering, the bioproduction process still remains costly. In order to expand the chemical repertoire for the production of next generation compounds, a major engineering biology effort is required in the development of novel design tools that target chemical diversity through rapid and predictable protocols. Addressing that goal involves retrosynthesis approaches that explore the chemical biosynthetic space. However, the complexity associated with the large combinatorial retrosynthesis design space has often been recognized as the main challenge hindering the approach. Here, we provide RetroPath2.0, an automated open source workflow for retrosynthesis based on generalized reaction rules that perform the retrosynthesis search from chassis to target through an efficient and well-controlled protocol. Its easiness of use and the versatility of its applications make of this tool a valuable addition into the biological engineer bench desk. We show through several examples the application of the workflow to biotechnological relevant problems, including the identification of alternative biosynthetic routes through enzyme promiscuity; or the development of biosensors. We demonstrate in that way the ability of the workflow to streamline retrosynthesis pathway design and its major role in reshaping the design, build, test and learn pipeline by driving the process toward the objective of optimizing bioproduction. The RetroPath2.0 workflow is built using tools developed by the bioinformatics and cheminformatics community, because it is open source we anticipate community contributions will likely expand further the features of the workflow.HighlightsState-of-the-art Computer-Aided Design retrosynthesis solutions lack open source and ease of useWe propose RetroPath2.0 a modular and open-source workflow to perform retrosynthesisRetroPath2.0 computes reaction network between Source and Sink sets of compoundsRetroPath2.0 is distributed as a KNIME workflow for desktop computersRetroPath2.0 is ready-for-use and distributed with reaction rulesFundingThis work was supported by the French National Research Agency [ANR-15-CE1-0008], the Biotechnology and Biological Sciences Research Council, Centre for synthetic biology of fine and speciality chemicals [BB/M017702/1]; Synthetic Biology Applications for Protective Materials [EP/N025504/1], and GIP Genopole.

scholarly journals Stochastic Simulations as a Tool for Assessing Signal Fidelity in Gene Expression in Synthetic Promoter Design

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 724
Author(s):  
Elena Righetti ◽  
Cansu Uluşeker ◽  
Ozan Kahramanoğulları
Keyword(s):  
Synthetic Biology ◽  
Computer Aided Design ◽  
Reaction Network ◽  
Intrinsic Noise ◽  
Stochastic Simulations ◽  
Fine Tuning ◽  
Promoter Strength ◽  
Synthetic Promoter ◽  
Synthetic Promoters ◽  
Noise Characteristics

The design and development of synthetic biology applications in a workflow often involve connecting modular components. Whereas computer-aided design tools are picking up in synthetic biology as in other areas of engineering, the methods for verifying the correct functioning of living technologies are still in their infancy. Especially, fine-tuning for the right promoter strength to match the design specifications is often a lengthy and expensive experimental process. In particular, the relationship between signal fidelity and noise in synthetic promoter design can be a key parameter that can affect the healthy functioning of the engineered organism. To this end, based on our previous work on synthetic promoters for the E. coli PhoBR two-component system, we make a case for using chemical reaction network models for computational verification of various promoter designs before a lab implementation. We provide an analysis of this system with extensive stochastic simulations at a single-cell level to assess the signal fidelity and noise relationship. We then show how quasi-steady-state analysis via ordinary differential equations can be used to navigate between models with different levels of detail. We compare stochastic simulations with our full and reduced models by using various metrics for assessing noise. Our analysis suggests that strong promoters with low unbinding rates can act as control tools for filtering out intrinsic noise in the PhoBR context. Our results confirm that even simpler models can be used to determine promoters with specific signal to noise characteristics.

scholarly journals SynBiopython: an open-source software library for Synthetic Biology

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jing Wui Yeoh ◽  
Neil Swainston ◽  
Peter Vegh ◽  
Valentin Zulkower ◽  
Pablo Carbonell ◽  
...  
Keyword(s):  
Synthetic Biology ◽  
Open Source ◽  
Open Source Software ◽  
Development Projects ◽  
Software Library ◽  
Current State ◽  
Starting Point ◽  
Common Problems ◽  
Data Tracking ◽  
Python Package

Abstract Advances in hardware automation in synthetic biology laboratories are not yet fully matched by those of their software counterparts. Such automated laboratories, now commonly called biofoundries, require software solutions that would help with many specialized tasks such as batch DNA design, sample and data tracking, and data analysis, among others. Typically, many of the challenges facing biofoundries are shared, yet there is frequent wheel-reinvention where many labs develop similar software solutions in parallel. In this article, we present the first attempt at creating a standardized, open-source Python package. A number of tools will be integrated and developed that we envisage will become the obvious starting point for software development projects within biofoundries globally. Specifically, we describe the current state of available software, present usage scenarios and case studies for common problems, and finally describe plans for future development. SynBiopython is publicly available at the following address: http://synbiopython.org.

scholarly journals Choosing Between Confocal Microscopes : A Fly-Eye's View

2000 ◽  
Vol 8 (3) ◽  
pp. 8-9
Author(s):  
Mark. H.C. Lam ◽  
David A. Jans
Keyword(s):  
Confocal Microscope ◽  
Ease Of Use ◽  
Image Manipulation ◽  
List Type ◽  
Type Number ◽  
Transmission Detector

We have recently been shopping for a confocal microscope and have found a simple way to test the capabilities of the various units that have been demonstrated to us. Some of the important aspects that we were looking for in our “ideal” multi-user system were:1)Ease of use.2)The ability to obtain good X-Y, X-Z and hence X-Y-Z resolution, and the accurate display of these images.3)The depth within the sample at which the system can resolve structures (this of course depends mostly on the lenses used), but is still an important criteria as it reflects on the system as a whole.4)“extras” such as a transmission detector and reconstruction/ analysis/image manipulation software.

How To Make a Glycopeptide: A Synthetic Biology Approach To Expand Antibiotic Chemical Diversity

2016 ◽  
Vol 2 (9) ◽  
pp. 642-650 ◽  
Author(s):  
Grace Yim ◽  
Wenliang Wang ◽  
Maulik N. Thaker ◽  
Stephanie Tan ◽  
Gerard D. Wright
Keyword(s):  
Synthetic Biology ◽  
Chemical Diversity ◽  
Synthetic Biology Approach

scholarly journals ABP para la enseñanza y desarrollo de proyectos tecnológicos interdisciplinares en Arduino [BPL for education and development of interdisciplinary technology projects based in Arduino]

2015 ◽  
Author(s):  
Yair Enrique Rivera Julio ◽  
Luis Gabriel Turizo Martínez
Keyword(s):  
Open Source ◽  
Collaborative Work ◽  
Project Based Learning ◽  
Ease Of Use ◽  
Resource Center ◽  
Building Technology ◽  
Technology Products ◽  
The Social ◽  
Teaching Learning ◽  
Education And Development

El presente trabajo muestra los resultados preliminares del proceso de enseñanza-aprendizaje para la generación de proyectos tecnológicos a través de la metodología de Aprendizaje Basado en Problemas (ABP), cuya importancia radica en la formación integral de los estudiantes en las áreas de programación y robótica constituida por una serie de pasos necesarios para una interacción secuencial y significativa que se originan en una simulación de software con arquitecturas open source como centro de aprendizaje didáctico, junto a una lluvia de ideas condicionadas en el aula de clase, diseñada para facilitar el uso de la electrónica en proyectos que permite diseñar prototipos de hardware basados en Arduino antes de ser armados físicamente. Al utilizar la metodología de aprendizajes ABP en la construcción de productos tecnológicos, se toman problemas planteados dentro del contexto social aplicando la enseñanza a través de temas avanzados como la robótica y la programación en sistemas, además de conjugar muchos aspectos dentro del sistema pedagógico en los proyectos tecnológicos a implementar donde se amerita el trabajo colaborativo, que es asumido dentro de sus integrantes como una conjugación de aspectos como la responsabilidad y las decisiones grupales.Palabras Clave: ABP (Aprendizaje Basado en Problemas), Arduino, prototipo, programación robótica.This work shows preliminary results of the PBL methodology in the teaching-learning process for generating Technological Projects, the importance lies in the comprehensive training of students in the areas of robotics and programming consists of a number of steps required for sequential and meaningful interaction originating from a software simulation with open source architectures as a learning resource center, next to brainstorm conditional on the classroom, designed for ease of use electronics technology projects allows us to design hardware prototypes based on Arduino before being physically armed. By using this method of learning in building technology products, problems are taken within the social context applying teaching through advanced topics such as robotics and programming systems, and combine many aspect in the pedagogical system projects implement technology where collaborative work, which is assumed within its members as a combination of aspects such as responsibility and group decisions is warranted.Keywords: PBL (Project Based Learning), Arduino, Prototype, Robotics programming.

scholarly journals chewBBACA: A complete suite for gene-by-gene schema creation and strain identification

2017 ◽  
Author(s):  
Mickael Silva ◽  
Miguel Machado ◽  
Diogo N. Silva ◽  
Mirko Rossi ◽  
Jacob Moran-Gilad ◽  
...  
Keyword(s):  
Open Source ◽  
Core Genome ◽  
Bacterial Species ◽  
Outbreak Detection ◽  
Strain Identification ◽  
List Type ◽  
Whole Genome ◽  
Link Type ◽  
The Creation ◽  
Allele Calling

ABSTRACTGene-by-gene approaches are becoming increasingly popular in bacterial genomic epidemiology and outbreak detection. However, there is a lack of open-source scalable software for schema definition and allele calling for these methodologies. The chewBBACA suite was designed to assist users in the creation and evaluation of novel whole-genome or core-genome gene-by-gene typing schemas and subsequent allele calling in bacterial strains of interest. The software can run in a laptop or in high performance clusters making it useful for both small laboratories and large reference centers. ChewBBACA is available athttps://github.com/B-UMMI/chewBBACAor as a docker image athttps://hub.docker.com/r/ummidock/chewbbaca/.DATA SUMMARYAssembled genomes used for the tutorial were downloaded from NCBI in August 2016 by selecting those submitted asStreptococcus agalactiaetaxon or sub-taxa. All the assemblies have been deposited as a zip file in FigShare (https://figshare.com/s/9cbe1d422805db54cd52), where a file with the original ftp link for each NCBI directory is also available.Code for the chewBBACA suite is available athttps://github.com/B-UMMI/chewBBACAwhile the tutorial example is found athttps://github.com/B-UMMI/chewBBACA_tutorial.I/We confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. ⊠IMPACT STATEMENTThe chewBBACA software offers a computational solution for the creation, evaluation and use of whole genome (wg) and core genome (cg) multilocus sequence typing (MLST) schemas. It allows researchers to develop wg/cgMLST schemes for any bacterial species from a set of genomes of interest. The alleles identified by chewBBACA correspond to potential coding sequences, possibly offering insights into the correspondence between the genetic variability identified and phenotypic variability. The software performs allele calling in a matter of seconds to minutes per strain in a laptop but is easily scalable for the analysis of large datasets of hundreds of thousands of strains using multiprocessing options. The chewBBACA software thus provides an efficient and freely available open source solution for gene-by-gene methods. Moreover, the ability to perform these tasks locally is desirable when the submission of raw data to a central repository or web services is hindered by data protection policies or ethical or legal concerns.

scholarly journals Computer Numerically Controlled Drawing Robot Based on Computer-Aided Design

2021 ◽  
Author(s):  
Antor Mahamudul Hashan ◽  
Abdullah Haidari ◽  
Srishti Saha ◽  
Titas Paul
Keyword(s):  
Open Source ◽  
Computer Aided Design ◽  
Low Cost ◽  
Rapid Development ◽  
Main Idea ◽  
Numerical Control ◽  
Computer Aided ◽  
Complex Circuits ◽  
Open Source Hardware ◽  
Aided Design

Due to the rapid development of technology, the use of numerically controlled machines in the industry is increasing. The main idea behind this paper is computer-aided design (CAD) based low-cost computer numerical control 2D drawing robot that can accurately draw complex circuits, diagrams, logos, etc. The system is created using open-source hardware and software, which makes it available at a low cost. The open-source LibreCAD application has been used for computer-aided design. Geometric data of a CAD model is converted to coordinate points using the python-based F-Engrave application. This system uses the Arduino UNO board as a signal generator of the universal g-code sender without compromising the performance. The proposed drawing robot is designed as a low-cost robot for educational purposes and aims to increase the student's interest in robotics and computer-aided design (CAD) skills to the next level. The drawing robot structure has been developed, and it meets the requirements of low cost with satisfactory experimental results.

scholarly journals Cell-free genetic devices confer autonomic and adaptive properties to hydrogels

2019 ◽  
Author(s):  
Colette J. Whitfield ◽  
Alice M. Banks ◽  
Gema Dura ◽  
John Love ◽  
Jonathan E. Fieldsend ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Information Processing ◽  
Synthetic Biology ◽  
Smart Materials ◽  
Living Organism ◽  
Chemical Diversity ◽  
Biological Information ◽  
Self Healing ◽  
Wide Range

AbstractSmart materials are able to alter one or more of their properties in response to defined stimuli. Our ability to design and create such materials, however, does not match the diversity and specificity of responses seen within the biological domain. We propose that relocation of molecular phenomena from living cells into hydrogels can be used to confer smart functionality to materials. We establish that cell-free protein synthesis can be conducted in agarose hydrogels, that gene expression occurs throughout the material and that co-expression of genes is possible. We demonstrate that gene expression can be controlled transcriptionally (using in gel gene interactions) and translationally in response to small molecule and nucleic acid triggers. We use this system to design and build a genetic device that can alter the structural property of its chassis material in response to exogenous stimuli. Importantly, we establish that a wide range of hydrogels are appropriate chassis for cell-free synthetic biology, meaning a designer may alter both the genetic and hydrogel components according to the requirements of a given application. We probe the relationship between the physical structure of the gel and in gel protein synthesis and reveal that the material itself may act as a macromolecular crowder enhancing protein synthesis. Given the extensive range of genetically encoded information processing networks in the living kingdom and the structural and chemical diversity of hydrogels, this work establishes a model by which cell-free synthetic biology can be used to create autonomic and adaptive materials.Significance statementSmart materials have the ability to change one or more of their properties (e.g. structure, shape or function) in response to specific triggers. They have applications ranging from light-sensitive sunglasses and drug delivery systems to shape-memory alloys and self-healing coatings. The ability to programme such materials, however, is basic compared to the ability of a living organism to observe, understand and respond to its environment. Here we demonstrate the relocation of biological information processing systems from cells to materials. We achieved this by operating small, programmable genetic devices outside the confines of a living cell and inside hydrogel matrices. These results establish a method for developing materials functionally enhanced with molecular machinery from biological systems.

scholarly journals Blueprints for Biosensors: Design, Limitations, and Applications

Genes ◽  
2018 ◽  
Vol 9 (8) ◽  
pp. 375 ◽  
Author(s):  
Alexander Carpenter ◽  
Ian Paulsen ◽  
Thomas Williams
Keyword(s):  
Transcription Factors ◽  
Synthetic Biology ◽  
Nucleic Acids ◽  
Dynamic Range ◽  
Optimal Performance ◽  
Ease Of Use ◽  
Ligand Specificity ◽  
Biotechnological Application ◽  
Wide Range ◽  
Output Time

Biosensors are enabling major advances in the field of analytics that are both facilitating and being facilitated by advances in synthetic biology. The ability of biosensors to rapidly and specifically detect a wide range of molecules makes them highly relevant to a range of industrial, medical, ecological, and scientific applications. Approaches to biosensor design are as diverse as their applications, with major biosensor classes including nucleic acids, proteins, and transcription factors. Each of these biosensor types has advantages and limitations based on the intended application, and the parameters that are required for optimal performance. Specifically, the choice of biosensor design must consider factors such as the ligand specificity, sensitivity, dynamic range, functional range, mode of output, time of activation, ease of use, and ease of engineering. This review discusses the rationale for designing the major classes of biosensor in the context of their limitations and assesses their suitability to different areas of biotechnological application.

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