Engineering Eco-Friendly and Sustainable Reflecting Crystals in Yeast to Replace Hazardous TiO2 Based Pigments

Project Information

CrystalCellFactory

Grant agreement ID: 101188091

DOI

10.3030/101188091

Project closed

EC signature date 23 July 2024

Start date 1 August 2024

End date 31 January 2026

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

WEIZMANN INSTITUTE OF SCIENCE
Israel

Periodic Reporting for period 1 - CrystalCellFactory (Engineering Eco-Friendly and Sustainable Reflecting Crystals in Yeast to Replace Hazardous TiO2 Based Pigments)

Reporting period: 2024-08-01 to 2026-01-31

Summary of the context and overall objectives of the project

Titanium dioxide (TiO2) has been widely used as a white pigment in food, cosmetics, and pharmaceuticals due to its excellent optical properties and stability. However, concerns regarding its potential health and environmental risks led to its ban as a food additive in the European Union in 2022. This regulatory shift has created an urgent need for safe, sustainable, and high-performance alternatives. Existing substitutes often fail to match TiO2 in terms of brightness, stability, and versatility, limiting their industrial adoption.

This project addresses this challenge by developing an innovative bio-based solution: the production of light-reflecting guanine crystals using genetically engineered yeast. In nature, guanine crystals are used by various organisms, such as fish, to efficiently reflect light and generate bright coloration. Inspired by these systems, the project leverages yeast as a scalable and environmentally friendly “cell factory” to produce such crystals as functional materials.
The main objective of the project was to demonstrate the feasibility of producing guanine crystals in yeast at levels suitable for replacing TiO2, while also assessing the commercial potential of this technology. Specifically, the project aimed to enhance guanine biosynthesis through metabolic engineering, optimize production efficiency, reduce unwanted by-products, and explore pathways toward industrial implementation.
By combining synthetic biology, metabolomics, and materials science, this project contributes to the development of safer and more sustainable ingredients aligned with European regulatory priorities and consumer demand.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The project implemented an integrated experimental and analytical approach to engineer yeast strains capable of efficiently producing guanine and forming reflective crystals.
On the technical side, genes involved in guanine biosynthesis were introduced into yeast to enhance the purine metabolic pathway. A dedicated metabolomic profiling platform based on liquid chromatography–mass spectrometry (LC-MS) was developed and applied to monitor pathway intermediates, quantify guanine levels, and identify metabolic bottlenecks.

This approach enabled iterative optimization of both genetic configurations and growth conditions. As a result, the project achieved a ~50-fold increase in guanine production compared to baseline levels, meeting the primary technical objective. Metabolic bottlenecks were identified at the level of inosine monophosphate (IMP), and targeted interventions, such as media supplementation,were implemented to alleviate these constraints.
In parallel, the accumulation of undesirable by-products, including uric acid and xanthine, was successfully controlled and reduced to approximately 10-fold lower levels, improving overall pathway efficiency and product purity.
Importantly, in selected yeast species, guanine crystal formation was observed both intracellularly and in the surrounding medium, providing key validation of the concept and demonstrating the feasibility of producing structured, functional materials in a biological system. The secretion of guanine into the medium further supports the scalability of the process by simplifying downstream recovery.

On the commercial side, initial market exploration confirmed strong demand for TiO2 alternatives, particularly in the European food sector. Preliminary discussions with relevant companies have been initiated, and ongoing engagement with the project’s commercialization partner is helping to refine the business strategy. These activities have contributed to advancing the project toward Technology Readiness Level (TRL) 4, demonstrating validation in a laboratory environment.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

This project advances beyond the current state of the art by introducing a fundamentally new paradigm for pigment production based on engineered biological systems. While existing alternatives to TiO2 rely on mineral or polymer-based materials with limited performance, this work demonstrates the feasibility of producing highly reflective crystalline materials through microbial biosynthesis.

A key innovation is the use of yeast to produce guanine, a molecule typically associated with essential cellular processes, as a building block for functional materials. This represents a novel convergence of synthetic biology and materials science, enabling the sustainable production of advanced materials with tunable properties. The observation of crystal formation within and outside the cells further distinguishes this approach from conventional biochemical production systems.
The results provide a strong foundation for future development and industrial translation. To ensure successful uptake, further work will focus on increasing production yields, improving process robustness, and validating material performance under application-relevant conditions. In addition, scaling up production and demonstrating consistency at pilot scale will be critical steps toward commercialization.

From a market perspective, continued engagement with industry stakeholders, strengthening of intellectual property, and access to follow-on funding will support the transition from laboratory validation to real-world applications. A supportive regulatory framework and alignment with sustainability-driven policies further enhance the potential for adoption.

In summary, the project delivers a promising, sustainable alternative to conventional pigments and establishes a clear pathway toward commercialization, with the potential to impact multiple industries including food, cosmetics, and pharmaceuticals.