Biology subjects

Carbonell, P.

Publications and source records attributed to Carbonell, P..

9 recordsLinked to original sources

bioRxiv2025

BiosInt: Biosensor-based smart design of pathway dynamic regulation for industrial biomanufacturing

Industrial-scale production of bio-based chemicals in the circular green bioeconomy still faces inefficiencies arising from scaling up challenges. Biosensor mediated control of metabolic pathways has been proposed as a strategy to improve the performance of those bioprocesses. By linking industrial biosynthetic pathways to measurable metabolites through biochemical transformations, a highly interconnected regulatory design space is unveiled, offering new opportunities for pathway dynamic control. Yet, a systematic approach for selecting and implementing genetic circuits within such large space has remained absent. Here, we introduce BiosInt, an allosteric transcription factor-based genetic biocircuit, with quasi-integral adaptation control capabilities that can be used to increase robustness and performance of biomanufacturing engineered strains. To test the capabilities of the circuit, we have analysed its performance for the full set of metabolic pathway topologies found in the bio-based chemical production space of compounds with industrial interest. For a given implementation of the BiosInt circuit, we carried out a multiobjective optimization process that provides the inverse control solution of optimal topology starting from any given pathway configuration and enzyme expression ratios. Next, synthetic datasets are generated to train machine learning-based predictive models with the data obtained from the simulations of each topology by varying enzyme expression levels and their corresponding concentrations. We validated the models by showing their ability to predict the best control topology for a given set of enzyme ratios. As a proof-of-concept, we show its application to the design of the genetic constructs expressing flavonoid production pathways, providing optimal performance for the BiosInt-mediated dynamic regulation. This circuit inverse design and its application to dynamic control in biomanufacturing paves the way for a future design pipeline in biofoundries delivering more robust and efficient sustainable bioproduction processes.

synthetic biology↗

bioRxiv2022

Sensbio: An online server for biosensor design

Allosteric transcription factor (aTF) based biosensors can be used to engineer genetic circuits for a wide range of applications. The literature and online databases contain hundreds of experimentally validated molecule-TF pairs, however the knowledge is scattered and often incomplete. Additionally, compared to the number of compounds that can potentially be produced using living systems, the number of those discovered with TF-based interactions is low. For these reasons, new tools that help researchers find new possible TF-ligand pairs are called for. In this work we present Sensbio (https://bit.ly/3OF4msH), an online web server that through similarity comparison against a TF-ligand reference database, is able to identify putative transcription factors that may be activated by a given input molecule. As a complement to the application, a predictive model has been developed to find new possible matches based on machine learning.

bioinformatics↗

bioRxiv2022

Galaxy-SynBioCAD: Automated Pipeline for Synthetic Biology Design and Engineering

We introduce the Galaxy-SynBioCAD portal, the first toolshed for synthetic biology, metabolic engineering, and industrial biotechnology. The tools and workflows currently shared on the portal enables one to build libraries of strains producing desired chemical targets covering an end-to-end metabolic pathway design and engineering process from the selection of strains and targets, the design of DNA parts to be assembled, to the generation of scripts driving liquid handlers for plasmid assembly and strain transformations. Standard formats like SBML and SBOL are used throughout to enforce the compatibility of the tools. In a study carried out at four different sites, we illustrate the link between pathway design and engineering with the building of a library of E. coli lycopene-producing strains. We also benchmarked our workflows on literature and expert validated pathways. Overall, we find an 83% success rate in retrieving the validated pathways among the top 10 pathways generated by the workflows.

synthetic biology↗

bioRxiv2021

Developing an enzyme selection tool supporting multiple hosts contexts

Engineering biological organisms that allow the integration of alternative metabolic pathways to natural ones is one of the goals of synthetic biology. Based on this, some of the most attractive applications in terms of synthetic organisms manufacture include the production of a wide range of pharmacologically useful metabolites produced in a sustainable and environmentally friendly way. Also, the biostable molecules green-production involves different types of therapeutic processes, e.g. prostheses and grafts stabilisation. Regarding the viability of genetically modified organisms, metabolic pathways must be first properly designed, taking into consideration the type of host organism that will be involved in metabolic production, as well as its biochemical and environmental conditions. To ensure the correct growth of these synthetic organisms, the enzyme selection must guarantee both the organism survival (and proliferation) and the optimal production of the desired metabolite. Developing enzyme selection tools is essential to enhance and make cost-effective the metabolic pathways design. This technical note presents the update of Selenzyme, the enzyme selection tool which is based on organisms taxonomic compatibility and allows appropriate enzyme selection considering its amino acid sequence. The purpose of the update is to allow multiple host input, in order to perform an affinity comparison between target organisms and each host. The affinity differences will depend on which host to be considered, allowing the user to select the optimal host for the enzyme concerned.

bioinformatics↗

bioRxiv2020

Galaxy-SynBioCAD: Synthetic Biology Design Automation tools in Galaxy workflows

Many computer-aided design tools are available for synthetic biology and metabolic engineering. Yet, these tools can be difficult to apprehend, sometimes requiring a level of expertise that limits their use by a wider community. Furthermore, some of the tools, although complementary, rely on different input and output formats and cannot communicate with one another. Scientific workflows address these shortcomings while offering a novel design strategy. Among the workflow systems available, Galaxy is a web-based platform for performing findable and accessible data analyses for all scientists regardless of their informatics expertise, along with interoperable and reproducible computations regardless of the particular platform that is being used. Here, we introduce the Galaxy-SynBioCADa portal, the first Galaxy toolshed for synthetic biology and metabolic engineering. It allows one to easily create workflows or use those already developed by the community. The portal is a growing community effort where developers can add new tools and users can evaluate the tools performing design for their specific projects. The tools and workflows currently shared on the Galaxy-SynBioCAD portal cover an end-to-end metabolic pathway design process from the selection of strain and target to the calculation of DNA parts to be assembled to build libraries of strains to be engineered to produce the target. Standard formats are used throughout to enforce the compatibility of the tools. These include SBML for strain and pathway and SBOL for genetic layouts. The portal has been benchmarked on 81 literature pathways, overall, we find we have a 65% (and 88%) success rate in retrieving the literature pathways among the top 10 (50) pathways predicted and generated by the workflows.

bioengineering↗

bioRxiv2017

Selenzyme: Enzyme selection tool for pathway design

Synthetic biology applies the principles of engineering to biology in order to create biological functionalities not seen before in nature. One of the most exciting applications of synthetic biology is the design of new organisms with the ability to produce valuable chemicals including pharmaceuticals and biomaterials in a greener; sustainable fashion. Selecting the right enzymes to catalyze each reaction step in order to produce a desired target compound is, however, not trivial. Here, we present Selenzyme, a free online enzyme selection tool for metabolic pathway design. The user is guided through several decision steps in order to shortlist the best candidates for a given pathway step. The tool graphically presents key information about enzymes based on existing databases and tools such as: similarity of sequences and of catalyzed reactions; phylogenetic distance between source organism and intended host species; multiple alignment highlighting conserved regions, predicted catalytic site, and active regions; and relevant properties such as predicted solubility and transmembrane regions. Selenzyme provides bespoke sequence selection for automated workflows in biofoundries. The tool is integrated as part of the pathway design stage into the design-build-test-learn SYNBIOCHEM pipeline. The Selenzyme web server is available at http://selenzyme.synbiochem.co.uk.

bioinformatics↗

bioRxiv2017

PartsGenie: an integrated tool for optimising and sharing synthetic biology parts

Synthetic biology is typified by developing novel genetic constructs from the assembly of reusable synthetic DNA parts, which contain one or more features such as promoters, ribosome binding sites, coding sequences and terminators. While repositories of such parts exist to promote their reuse, there is still a need to design novel parts from scratch.\n\nPartsGenie, freely available at http://parts.synbiochem.co.uk, is introduced to facilitate the computational design of such synthetic biology parts. PartsGenie has been designed to bridge the gap between optimisation tools for the design of novel parts, the representation of such parts in community-developed data standards such as Synthetic Biology Open Language (SBOL), and their sharing in journal-recommended data repositories.\n\nConsisting of a drag-and-drop web interface, a number of DNA optimisation algorithms, and an interface to the well-used data repository JBEI ICE, PartsGenie facilitates the design, optimisation and dissemination of reusable synthetic biology parts through a single, integrated application. PartsGenie can therefore be used as a single, stand-alone tool, or integrated into larger synthetic biology pipelines that are being developed in the SYNBIOCHEM centre and elsewhere.

synthetic biology↗

bioRxiv2017

Molecular structures enumeration and virtual screening in the chemical space with RetroPath2.0

BackgroundNetwork generation tools coupled with chemical reaction rules have been mainly developed for synthesis planning and more recently for metabolic engineering. Using the same core algorithm, these tools apply a set of rules to a source set of compounds, stopping when a sink set of compounds has been produced. When using the appropriate sink, source and rules, this core algorithm can be used for a variety of applications beyond those it has been developed for.\n\nResultsHere, we showcase the use of the open source workflow RetroPath2.0. First, we mathematically prove that we can generate all structural isomers of a molecule using a reduced set of reaction rules. We then use this enumeration strategy to screen the chemical space around a set of monomers and predict their glass transition temperatures, as well as around aminoglycosides to search structures maximizing antibacterial activity. We also perform a screening around aminoglycosides with enzymatic reaction rules to ensure biosynthetic accessibility. We finally use our workflow on an E. coli model to complete E. coli metabolome, with novel molecules generated using promiscuous enzymatic reaction rules. These novel molecules are searched on the MS spectra of an E. coli cell lysate interfacing our workflow with OpenMS through the KNIME analytics platform.\n\nConclusionWe provide an easy to use and modify, modular, and open-source workflow. We demonstrate its versatility through a variety of use cases including, molecular structure enumeration, virtual screening in the chemical space, and metabolome completion. Because it is open source and freely available on MyExperiment.org, workflow community contributions should likely expand further the features of the tool, even beyond the use cases presented in the paper.

systems biology↗

bioRxiv2017

RetroPath2.0: A retrosynthesis workflow for metabolic engineers

Synthetic 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.\n\nHighlightsO_LIState-of-the-art Computer-Aided Design retrosynthesis solutions lack open source and ease of use\nC_LIO_LIWe propose RetroPath2.0 a modular and open-source workflow to perform retrosynthesis\nC_LIO_LIRetroPath2.0 computes reaction network between Source and Sink sets of compounds\nC_LIO_LIRetroPath2.0 is distributed as a KNIME workflow for desktop computers\nC_LIO_LIRetroPath2.0 is ready-for-use and distributed with reaction rules\nC_LI\n\nFundingThis 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.

systems biology↗