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iCulture: A digital bio-platform and co-culture bioprocess to prospect and utilize macroalgae responsibly and sustainably.

Periodic Reporting for period 1 - iCULTURE (iCulture: A digital bio-platform and co-culture bioprocess to prospect and utilize macroalgae responsibly and sustainably.)

Reporting period: 2023-09-01 to 2025-02-28

Over 100 Megatons of seaweed constitute Europe's largest biomass, but less than 0.25% is utilized. Marine industry stakeholders are currently left with 50-70% of residual side-streams sold as low-cost fertilizers. Existing data on more than 10000 macroalgae species could help this industry to improve their processes but the data is too large and manual curation is not feasible. Despite the progression of artificial intelligence (A.I.) and digital instruments, these techniques have barely entered the bio-based sector.

iCulture is a cross-disciplinary consortium where European expertise on ICT, bioinformatic, biodiversity, biotechnology, synthetic biology and bioprocessing is combined to develop a set of digital toolboxes that can prospect for new species of seaweed, utilize these in microbial fermentation, and understand how to use it responsibly and sustainably. Over 80 TB of existing seaweed data and 700.000 genes will be mined by machine learning algorithms in an A.I. toolbox to identify macroalgae characteristics: growth, response to environmental conditions, chemical composition and more. These will be used by a predictive Model toolbox, with models for compositional changes, recovery, resilience and Dispersion, to deliver key features that are important for responsible resource management. A Bioprocess technology toolbox will use this information for a machine learning controlled microbial co-culture, that will convert complex sugar mixtures to catalysts producing high-value antimicrobials. The multiple benefits of this digital platform are 1) boost the prospecting efficiency of new species by using powerful A.I. algorithms 2) help to understand the potential and vulnerability of resources, so that a responsible management strategy can guide the operations of stakeholders, and 3) create a novel value-chain, valorizing European seaweed side-streams into valuable antimicrobials (>$150/kg) for feed, food and pharma, while reducing CO2 footprint more than 20%.
The main activities were focused on:
1. creation of engineered microbial cells that can consume seaweed components
2. Development of process of fermentation designated for the seaweed
3. Analyzing the seaweed in dedicated laboratories, including mass spectroscopy and chromatography. Analyzing the composition of the seaweed.
4. curation of large amount of data on the seaweed, including dispersion, growth, and composition, sorting the data, labeling the data and packing the data into a database suitable for machine learning mining tools. This database will be published open access (e.g. Zenodo platform) during year 4 of the project.
5. Exploring the data with machine learning tools to understand features of seaweed, including composition and growth, and short listing the seaweed into categories that are of importance to the industry.

The main achievements are
1. creation of a large database of the European seaweed that contains important information for seaweed preservation and utilization. This database will be made available for open access once completed, validated and verified at year 4 of the project.
2. identified several seaweed species that are of importance for the industry, and understanding their chemical composition. This results are currently disseminated in scientific and other publications.
3. developing cell factories that can be utilize large parts of the seaweed and grow on these. This cell factories are the basis for the fermentation process. We will continue to improve these cell factories.
4, developed automated process that controls microbial growth. This automated process will be later compiled to a "toolbox" that can be used by the bio-processing community for fermentation control of second generation feedstock.
• By applying machine learning and deep learning algorithms alongside causality analysis techniques, iCulture creates predictive models that vastly improve the efficiency of prospecting new seaweed species and help forecast environmental responses, enabling a responsible management strategy for sustainable harvesting.

• iCulture’s novel design of bacterial “cell factories” employs a modular architecture built on orthogonal genetic “bricks”. By engineering strains that can utilize seaweed-derived sugars with nearly complete (up to 90–100%) substrate conversion, these microbial platforms outperform traditional systems, which typically show lower efficiency. This modular approach not only enables flexibility in targeting different sugars but also ensures reproducibility and scalability in production processes.

• The development of a co-culture bioprocess that uses an integrated digital twin system, together with both model predictive (MPC) and the emerging reinforcement learning (RL) controllers. This system continuously monitors and adjusts process parameters in near real time via advanced biosensor integration to stabilize and optimize co-culture dynamics. Such a strategy enables the conversion of complex seaweed sugar mixtures into high-value antimicrobial compounds at improved yields and reduced carbon footprints—surpassing conventional fermentation methods. The RL is still under development, we will continue to work on the RL control strategy until validation.

• Complementing the biological advances, iCulture has also demonstrated optimized hydrolysis methods for seaweed biomass that maximize the release of fermentable monosaccharides. By fine-tuning key parameters such as pH, temperature, acid concentration, and biomass loading, the project has achieved yields that are considerably higher than those traditionally reported (over 20% higher). The full results will be published in relevant journals. This enhanced process adaptability ensures that even the underutilized side-streams of seaweed biomass can be efficiently valorized, providing economic and environmental benefits.
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