Team:DTU-Denmark/Description

• The problem: A world under stress
• Biotechnology - a possible solution
• Filamentous fungi - our tools
• RESHAPE - our solution
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The problem: A world under stress

The climate continually reaches new extremes and to break this vicious circle of our own creation, we must change many aspects of our daily lives. Sustainable choices must be made at all levels, from the individual to global governing and commercial organisations, as clearly communicated by the UN sustainability goals. However, options for individuals are often limited by the availability of sustainable products. Reconfiguring production towards greater sustainability will therefore be paramount to overcoming the challenges currently facing the world.

Biotechnology - a possible solution

To reach the UN sustainability goals, industrial production practices will have to change so as to reduce the carbon footprint related to the production of a vast array of products used around the world. Synthetic biology offers an avenue for making these changes and can therefore assist in reducing the climate impact by increasing the sustainability of many products (Meyer et al., 2016).

White biotechnology is a multi-billion dollar industry. In 2015 alone, the global demand was estimated at 203 billion USD and it is rising (White Biotechnology Market Size | Industry Report, 2024, 2020). Filamentous fungi account for a large proportion of production of enzymes and chemicals, with Aspergillus being responsible for 60% of all industrial enzyme production (Siddiqui, 2016). In addition, filamentous fungi and other microorganisms provide a sustainable alternative to many existing petroleum-based production methods. However, higher production costs currently act as a deterrent for shifting production in this direction. We wanted to create tools to make this shift more feasible.

Filamentous fungi - our tools

Filamentous fungi arrange their cells in thread-like, multicellular networks called mycelia. Depending on genetic and environmental parameters, the networks can take on different shapes or morphologies. This allows filamentous fungi to colonise substrates in an energy efficient manner by covering a substrate with the least amount of biomass possible. Filamentous fungi have incredible secretory capacity due to specialized organs, named hyphal tips, which can secrete more than 30.000 vesicles per minute (Meyer et al., 2016 ; Steinberg, 2007). These traits make filamentous fungi interesting from an industrial standpoint while presenting their own set of challenges. The filaments of filamentous fungi increase viscosity in fermentation tanks, limiting oxygen transfer to the cells, stressing the cells, and ultimately leading to decreased productivity (Arnau, Yaver and Hjort, 2020). Therefore, any improvement of morphology in this species has the potential to have a tremendous positive impact on production.

An untapped solution is to utilize the power of synthetic biology to control the morphology of filamentous fungi. A study from 2016 showed that a change in morphology could cause a 66% increase in secreted enzyme product (He et al., 2016). For some products, evenly dispersed mycelial growth leads to improved production, while for others mycelia growing in dense “pellets” is preferable (Cairns et al., 2019). As such, controlling the morphology could be of great use in industrial applications. Our solution would provide molecular tools for academia and industry to ensure a morphology that fits the product of interest.

RESHAPE - our solution

We RESHAPE mycelial morphology in filamentous fungi to aid industrial production of proteins and small molecules. This is done by identifying genetic targets in Aspergillus niger which can be engineered in most industrially relevant strains of the species using synthetic biology.

We also develop novel signal peptides to improve protein secretion in A. niger. Finally we develop software tools which may predict morphology patterns of filamentous fungi and create synthetic signal peptides which can increase protein secretion levels. Improving the efficiency of bio-based production processes will provide economic incentives to use them. In this way, we can decrease our reliance on oil-based substrates and move towards a more sustainable and bio-based future.