H2020 Rafts4Biotech Project: Synthetic bacterial lipid rafts to optimize industrial bioprocesses
- Type Project
- Status Filled
- Execution 2017 -2021
- Assigned Budget 6.733.580,00 €
- Scope Europeo
- Main source of financing H2020
- Project website Rafts4Biotech
Rafts4Biotech is a 48-month research project that will be developed by a well-balanced consortium of three RTOs, four universities, and five SMEs.
The methodology required to develop the Rafts4Biotech proposal is based on an integrated systems biology approach combined with several distinct disciplines, such as mathematical modeling, enzymology, and synthetic biology approaches. This multifaceted disciplinary aspect of the Rafts4Biotech consortium is a consequence of our conviction to develop synthetic bacterial lipid rafts as an innovative technology with broad industrial applications.
The work packages (WPs) described below in this proposal aim to demonstrate the versatility of our technology by addressing three important biotechnological conundrums caused by the current metabolic limitations suffered by conventional microbial chassis:
- Engineering cell factories to produce new lipophilic antibiotics that are difficult to produce under laboratory conditions (Pharma-SC).
- Implement existing cell factories to produce cosmetic additives that currently show low production yields and high production costs (Cosmetics-SC) and
- Develop more robust and resilient cellular factories to remove industrial contaminants from food and beverage sources (Feed-SC).
The genetic tractability of bacterial cells allows for the generation of synthetic microbial chassis platforms (SMCPs) with significant biotechnological applications. However, their functionality currently faces significant extragenomic limitations due to poor protein-protein interactions, unfavorable protein stoichiometry, and the generation of toxic intermediates that ultimately compromise industrial production processes.
To address this issue, the Rafts4Biotech project will leverage our recent discovery: bacteria are capable of organizing subcellular membrane compartments similar to the lipid rafts of eukaryotic cells to enhance/protect specific cellular processes. The Rafts4Biotech project will engineer bacterial cells to confine biotechnologically relevant reactions within bacterial lipid rafts, optimizing their stoichiometry and protecting the cells from undesirable metabolic interference.
Therefore, the Rafts4Biotech project will produce reliable and robust next-generation SMCPs, in which industrial production processes are confined within bacterial lipid rafts, freed from their classic extragenomic constraints and optimized for industrial production. Furthermore, this concept can be applied to many prokaryotes, as lipid rafts are present in many bacterial species.
Building on this versatility, the Rafts4Biotech project will utilize two biotechnologically relevant biosystems, Bacillus subtilis and Escherichia coli, to engineer synthetic bacterial lipid rafts to optimize the performance of three complex biochemical processes in the pharmaceutical, cosmetic, and animal feed industries.
To achieve this, the Rafts4Biotech consortium combines diverse expertise in synthetic biology, systems biology, and mathematical modeling, and includes several SMEs that will actively work on this project and translate this technology into commercial applications. The technology developed by Rafts4Biotech will optimize multi-stage industrial processes and boost European research.
Social impact: The R4B project will develop high-value products that will contribute to creating a positive public opinion about synthetic and systems biology. Furthermore, Rafts4Biotech does not plan to release any constructs to the open environment, so we anticipate a positive reception for this project among all social and industrial biotechnology stakeholders, thus contributing to improving public opinion about biotechnology and synthetic biology.
General objective: R4B will develop a versatile new generation of microbial chassis to confine industrially relevant reactions within newly discovered subcellular membrane compartments called bacterial lipid rafts. This will enable precise regulation of industrial processes, their optimal performance, and their isolation from cellular metabolism to prevent toxic reactivity.
The genetic tractability of bacterial cells allows for the generation of synthetic microbial chassis platforms (SMCPs) with significant biotechnological applications. However, their functionality currently faces significant extragenomic limitations due to poor protein-protein interactions, unfavorable protein stoichiometry, and the generation of toxic intermediates that ultimately compromise industrial production processes.
To address this issue, the Rafts4Biotech project will leverage our recent discovery: bacteria are capable of organizing subcellular membrane compartments similar to the lipid rafts of eukaryotic cells to enhance/protect specific cellular processes. The Rafts4Biotech project will engineer bacterial cells to confine biotechnologically relevant reactions within bacterial lipid rafts, optimizing their stoichiometry and protecting the cells from undesirable metabolic interference.
Therefore, the Rafts4Biotech project will produce reliable and robust next-generation SMCPs, in which industrial production processes are confined within bacterial lipid rafts, freed from their classic extragenomic constraints and optimized for industrial production. Furthermore, this concept can be applied to numerous prokaryotes, as lipid rafts are found in numerous bacterial species.
Building on this versatility, the Raft4Biotech project will use two biotechnologically relevant biosystems, Bacillus subtilis and Escherichia coli, to design synthetic bacterial lipid rafts and optimize the performance of three complex biochemical processes in the pharmaceutical, cosmetic, and animal feed sectors.
To achieve this, the Rafts4Biotech consortium combines diverse expertise in synthetic biology, systems biology, and mathematical modeling, and includes several SMEs that will actively work on this project and translate this technology into commercial applications. The technology developed by Rafts4Biotech will optimize multi-stage industrial processes and boost European research.
The genetic tractability of bacterial cells allows for the generation of synthetic microbial chassis platforms (SMCPs) that express complex genetic circuits with significant biotechnological applications. Despite their genetic versatility, the proper functionality of SMCPs currently faces significant extragenomic limitations due to poor protein-protein interactions, unfavorable protein stoichiometry, and the generation of toxic intermediates that interfere with metabolism and ultimately compromise industrial production processes. Overcoming these limitations is one of the most significant challenges of synthetic biology for the implementation of artificial biosystems. The Rafts4Biotech project seeks to address this obstacle.
The innovation component of the Rafts4Biotech project is based on our recent discovery that bacteria are capable of organizing specific subcellular membrane compartments, similar to the so-called lipid rafts of eukaryotic cells, to improve the efficiency of specific cellular processes and protect them from cross-reactions outside of bacterial lipid rafts. Based on this discovery, it may be possible to engineer bacterial cells to confine biotechnologically relevant reactions within lipid rafts, thereby optimizing their stoichiometry and protecting them from undesirable metabolic interference.
The Rafts4Biotech project will implement this novel technology and produce a new generation of reliable and robust SMCPs, in which industrial production processes are confined within bacterial lipid rafts. Thanks to this new technology, SMCPs will overcome their classic limitations outside the genome and will be optimized for industrial production. Furthermore, these new artificial biosystems can select for and against a wide variety of biological interactions and produce an extremely adaptable microbial chassis for the production of a wide and diverse group of value-added products. Furthermore, limiting interactions with cellular metabolism will increase the robustness of cell factories, as it will protect cells from undesirable reactions and, consequently, from the accumulation of toxic intermediates.
It is important to highlight that the scientific concept we will develop in the Rafts4Biotech proposal can be applied to a huge variety of prokaryotes that are used, conventionally or unconventionally, as microbial chassis in industrial settings. This is because the existence of bacterial lipid rafts has been detected in almost all bacterial species. Based on the versatility of this new technology, the Raft4Biotech project will use two biotechnologically relevant microbial systems: the Gram-positive bacterium Bacillus subtilis and the Gram-negative bacterium Escherichia coli, to design synthetic bacterial lipid rafts to optimize the performance of three complex biochemical processes of growing biotechnological interest. These will be used as case studies for the implementation of this proposal and are detailed below:
- Production of new antibiotics to combat resistant infections (Pharma-SC case study)
- Implementation of commercially valuable biochemical pathways (Cosmetics case study or Cosmetics-SC)
- Improving microbial chassis to withstand aggressive industrial processes (Food Case Study or Feed-SC)
- CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS (CSIC)
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