Public deliverables will be made available below as soon as they are complete:

WP1: Project Management - led by SilicoLife

•  D1.4: Final project report to the European Commission - due MONTH 48
  

WP2: Retrosynthesis & Enumeration - led by SilicoLife

•  D2.4: Pathway database with all ranking and analysis metrics - due MONTH 36
  

WP3: Chemical Synthesis of New Products - led by GalChimia

•  No public deliverables
  

WP4: Gene Discovery & Protein Engineering - led by Universidade NOVA de Lisboa

•  No public deliverable

WP5: In Silico Metabolic Engineering - led by EMBL

• D.5.5: Public Final version of the updated models, due MONTH 42
  

WP6: Pathway Screening - led by University of Manchester

•  No public deliverables
  

WP7: Cell Factory Construction - led by DTU

•  No public deliverables

WP8: Product Validation & Sustainability Appraisal - led by DSM

•  D8.5: Sustainability appraisal and risk assessment of 10 target molecules, due MONTH 48
  

WP9: Exploitation and Dissemination - led by NNFCC

• D9.2: Project visuals and messaging - COMPLETED MONTH 6

• D9.3: Communication Channels (Website, Twitter, LinkedIn) - COMPLETED MONTH 6

Below is a collection of resources used to promote and disseminate information associated with the ShikiFactory100 project. 

Project video - a short video explaining the scope of the project in more detail. It can also be accompanied by English, Spanish and Portuguese subtitles.

Newsletter 01 - welcome to the first Shikifactory100 Newsletter!. Here, we aim to update you on all the progress made by our partners so far.

Project Leaflet  - contains general information about the project and describes its three major vectors (discovery, design & implementation, and validation).

Roll-up Banner - for project promotion at events such as conferences and trade fairs. 

Newsletter 02 - welcome to the final Shikifactory100 Newsletter! Here, we aim to update you on all the progress made by our partners.

Project Articles

Shikimate pathway - this article aims to provide background information about the research carried out by the project. It describes key metabolic pathways for living organisms, including the shikimate pathway, central to the Shikifactory100 project, and their applications at an industrial level.

Synthetic Biology for the Production of Biobased Molecules - this article aims to provide a background to the field of synthetic biology.  

Business plans for the Shikifactory100 project - this article gives more details about ShikiFactory100's business model and business plan.

Synthetic biology, sustainability and the circular bioeconomy - this article explores the process of transitioning towards a sustainable biobased bioeconomy.

Molecule Cards

As part of the ShikiFactory100 social media campaign, we have created molecule cards that introduce some of the 100 compounds the ShikiFactory project is working on. As these cards are posted on Twitter and LinkedIn, they will be made available on our website in the space below.

• Robinson, C. J., et al., (2020). Rapid prototyping of microbial production strains for the biomanufacture of potential materials monomers. Metabolic Engineering. 60, 168-182.

Synthetic biology can provide an alternative method for the production of bio-based industrial chemicals. But constructing the engineered microbial strains required for producing new chemicals can be time consuming. In this paper, the authors try to quantify the time requirements, on the basis of a state-of-the-art semi-automated strain engineering platform, using a collection of monomers for biomaterial production as their test case.

• Milne, N., et al., (2020). Metabolic engineering of Saccharomyces cerevisiae for the de novo production of psilocybin and related tryptamine derivatives. Metabolic Engineering. 60, 25-36.

Psylocibin is a compound most famously found in “magic mushrooms”. It has potent psychotropic properties, which aside from its notorious recreational uses, is also thought to hold potential for the treatment of a range of psychological and neurological ailments. In their study, Milne et al demonstrate that psylocibin could be produced using engineered yeast Saccharomyces cerevisiae. Furthermore, the yeast could produce psilocybin derivatives that may have new useful pharmaceutical properties.

• Vieira, V., Rocha, M., (2019). CoBAMP: a Python framework for metabolic pathway analysis in constraint-based models. Bioinformatics. 35(24), 5361–5362. 

• Grozinger, L., et al., (2019). Pathways to cellular supremacy in biocomputing. Nature Communications. 10(5250).

• Borja, G. M., et al., (2019). Metabolic engineering and transcriptomic analysis of Saccharomyces cerevisiae producing p-coumaric acid from xylose. Microbial Cell Factories. 18(191).

Aromatic amino acids are valuable chemicals and are precursors for a range of industrial compounds. This particular study looks at p-coumaric acid, which is a central precursor for many aromatic secondary metabolites, and aims to improve its production in yeast. Borja et al observed a significant effect that the carbon source had on the production, where xylose was a better substrate for p-coumaric acid production than glucose.

• Del Carratore, F., et al., (2019). Integrated Probabilistic Annotation: A Bayesian-Based Annotation Method for Metabolomic Profiles Integrating Biochemical Connections, Isotope Patterns, and Adduct Relationships. Analytical Chemistry. 91(20), 12799–12807. 

The comprehensive study of metabolites within cells, biofluids and tissues, referred to as metabolomics, often generates huge amounts of complex data generated by mass spectrometry. Identifying specific metabolites from such large amounts of data is a major challenge faced by researchers running metabolomics experiments. In this paper, Del Carratore et al. describe a new annotation method, explaining how the annotations are being applied and how to evaluate the confidence of the resulting annotations.

• Currin, A., et al., (2019). Highly multiplexed, fast and accurate nanopore sequencing for verification of synthetic DNA constructs and sequence libraries. Synthetic Biology. 4(1). 

The need for efficient DNA construction methods is inherent to the field of Synthetic Biology. With this comes the need to verify the accuracy and quality of the engineered DNA through high-precision sequencing methods. In this paper, the researchers outline an innovative methodology that will enable newly constructed DNA samples to be sequenced and verified accurately and cheaply.

• Cruz F., et al., (2020) Towards the Reconstruction of Integrated Genome-Scale Models of Metabolism and Gene Expression. In: Fdez-Riverola F., Rocha M., Mohamad M., Zaki N., Castellanos-Garzón J. (eds) Practical Applications of Computational Biology and Bioinformatics, 13th International Conference. PACBB 2019. Advances in Intelligent Systems and Computing, vol 1005. Springer, Cham. 

• Correia, J., et al., (2019). Artificial Intelligence in Biological Activity Prediction.  In: Fdez-Riverola F., Rocha M., Mohamad M., Zaki N., Castellanos-Garzón J. (eds) Practical Applications of Computational Biology and Bioinformatics, 13th International Conference. PACBB 2019. Advances in Intelligent Systems and Computing, vol 1005. Springer, Cham. 

• Vieira, V., et al., (2019). Comparison of pathway analysis and constraint-based methods for cell factory design. BMC Bioinformatics. 20(350). 

• Carbonell, P., et al., (2019). Efficient learning in metabolic pathway designs through optimal assembling. IFAC PapersOnLine. 52(26), 7-12.
  
  
• Babaei M., et al., (2020). Metabolic engineering of Saccharomyces cerevisiae for rosmarinic acid production. ACS Synth Biol. 9(8), 1978-1988.

Rosmarinic acid is a compound found in several plants. It is widely used as a food and cosmetic ingredient and has various pharmaceutical applications. However the production of this compound remains limited as natural availability is low and chemical synthesis is too complex. This study, for the first time, shows recombinant production of rosmarinic acid in engineered yeast.

• Sáez-Sáez J., et al., (2020). Engineering the oleaginous yeast Yarrowia lipolytica for high-level resveratrol production. Metab Eng. 62, 51-61.

Resveratrol is a plant secondary metabolite with a range of medicinal properties. Its low availability from the plants has led researchers to develop microbial production of the compound, however commercially viable production levels are still proving difficult. In this study, the authors demonstrated that Yarrowia lipolytica is a promising host for the production of resveratrol along with several other valuable products.

• Otero-Muras, I., Carbonell, P., (2020). Automated engineering of synthetic metabolic pathways for efficient biomanufacturing. Metab Eng. [Online ahead of print]

Metabolic engineering involves the engineering and optimization of processes from single-cell to fermentation in order to increase production of valuable chemicals. Significant advances in strain engineering are leading metabolic engineering to become a truly manufacturing technology capable of producing goods on an industrial scale. This review article demonstrates that the success of metabolic engineering heavily relies on biodesign algorithms which identify promising production routes and regulation strategies.

• Carbonell, P., et al., (2020). In silico design and automated learning to boost next-generation smart biomanufacturing. Synthetic Biology. 5(1).  

The increasing demand for bio-based compounds is now allowing biofoundries to produce and deliver valuable goods on an industrial scale. Nowadays, entire portfolios of producer strains are being developed in record times thanks to the integration and automation of the design, build, test and learn (DBTL) steps of the production cycle. As new in silico design tools are being developed to improve the efficacy of DBTL pipelines, the ever-increasing data gathered by biofoundries can now be added to these in-silico tools, therefore rendering them even more powerful and reliable. This paper discusses the future of biomanufacturing in an environment where the process will not only be fully automated, but will also be able to learn and adapt quickly to produce optimal designs.

• Dunstan, MS., et al., (2020). Engineering Escherichia coli towards de novo production of gatekeeper (2S)-flavanones: naringenin, pinocembrin, eriodictyol and homoeriodictyol. Synthetic Biology. 5(1).

• Choudhury, S., et al., (2022). Reconstructing kinetic models for dynamical studies of metabolism using generative adversarial networks. Nature Machine Intelligence. 4: 710-719.

• Oftadeh, O., et al., (2021). A genome-scale metabolic model of Saccharomyces cerevisiae that integrates expression constraints and reaction thermodynamics. Nature Communications. 12.
  
  
• Mohammadi-Peyhani, H., et al., (2021). Expanding biochemical knowledge and illuminating metabolic dark matter with ATLASx. Nature Communications. 13.
  
  
• Sveshnikova, A., et al., (2021). ARBRE: Computational resource to predict pathways towards industrially important aromatic compounds. Metabolic Engineering. 72.
  
  
• Weilandt, D.R., et al., (2022). Symbolic Kinetic Models in Python (SKiMpy): Intuitive modeling of large-scale biological kinetic models. Bioinformatics. 39.
  
  
• Sousa, T., et al., (2021). Generative deep learning for targeted compound design. Journal of Chemical Information and Modeling. 61(11).
  
  
• Pereira, V. & Rocha, M., (2021). Combinatorial Optimization of Succinate Production in Escherichia coli. International Conference on Practical Applications of Computational Biology & Bioinformatics.
  
  
• Pereira, V., et al., (2021). MEWpy: a computational strain optimization workbench in Python. Bioinformatics. 37(16).
  
  
• Sousa, T., (2021). Combining Multi-objective Evolutionary Algorithms with Deep Generative Models Towards Focused Molecular Design. Applications of Evolutionary Computation: 24th International Conference, EvoApplications 2021, Held as Part of EvoStar 2021, Virtual Event, April 7–9, 2021, Proceedings.
  
  
• Carbonell, A., (2021). A retrobiosynthetic approach for production, conversion, sensing, dynamic regulation and degradation of molecules. New Frontiers and Applications of Synthetic Biology.
  
  
• Del Carratore, F., et al., (2022). Biotechnological application of Streptomyces for the production of clinical drugs and other bioactive molecules. Current Opinion in Biotechnology.

• Narayanan, B., et al., (2022). Rational strain design with minimal phenotype perturbation. BioRxiv.
  
  
• Subham, C., et al., (2023). Generative machine learning produces kinetic models that accurately characterize intracellular metabolic states. BioRxiv.
  
  
• Hanko, E., et al., (2023). TFBMiner: A User-Friendly Command Line Tool for the Rapid Mining of Transcription Factor-Based Biosensors. ACS Synthetic Biology.

• Milne, N., et al., (2023). Engineering Saccharomyces cerevisiae for the de novo Production of Halogenated Tryptophan and Tryptamine Derivatives. Chemistry Open. 12(4).

• Ramos-Viana, V., et al., (2022). Modulation of the cell wall protein Ecm33p in yeast Saccharomyces cerevisiae improves the production of small metabolites. FEMS Yeast Research. 22(1).

• Costa, CE., et al., (2022). Valorisation of wine wastes by de novo biosynthesis of resveratrol using a recombinant xylose-consuming industrial Saccharomyces cerevisiae strain. Green Chemistry. 23.
  

Scientific results from the ShikiFactory100 project will also be made available via CORDIS (Community Research and Development Information Service, the European Commission's public repository for the dissemination of information from all EU-funded research projects.

Results are to be stored and shared between partners via the ICE and GitLab platforms.