Universal law for diffusive mass transport through mycelial networks

Abstract

Filamentous fungal cell factories play a pivotal role in biotechnology and circular economy. Hyphal growth and macroscopic morphology are critical for product titers; however, these are difficult to control and predict. Usually pellets, which are dense networks of branched hyphae, are formed during industrial cultivations. They are nutrient‐ and oxygen‐depleted in their core due to limited diffusive mass transport, which compromises productivity of bioprocesses. Here, we demonstrate that a generalized law for diffusive mass transport exists for filamentous fungal pellets. Diffusion computations were conducted based on three‐dimensional X‐ray microtomography measurements of 66 pellets originating from four industrially exploited filamentous fungi and based on 3125 Monte Carlo simulated pellets. Our data show that the diffusion hindrance factor follows a scaling law with respect to the solid hyphal fraction. This law can be harnessed to predict diffusion of nutrients, oxygen, and secreted metabolites in any filamentous pellets and will thus advance the rational design of pellet morphologies on genetic and process levels.

Understanding and controlling filamentous growth of fungal cell factories: novel tools and opportunities for targeted morphology engineering

“…In addition to the µCT assessment of real pellets from five industrial strains, it became also possible to compute such structures via Monte-Carlo growth simulations from scratch. The large set of computer-generated mycelial structures (> 3000) confirmed the generalised correlation of the effective diffusion coefficient with the porosity [ 31 ].…”

“…With respect to modelling, a seamless multiscale integration of various approaches will become possible. Subcellular models form the basis of branching rates and branching directions to be used in Monte-Carlo simulations of pellet formation [ 31 , 49 , 50 ]. Such single pellet information needs to be transferred to a bioreactor scale, where the heterogeneity of different pellets with respect to pellet diameter, aspect ratio and surface solidity need to be accounted for.…”

Applicability of a single‐use bioreactor compared to a glass bioreactor for the fermentation of filamentous fungi and evaluation of the reproducibility of growth in pellet form

“…A comprehensive study about the correlation between morphology and mass transport in filamentous fungi pellets is also available, written by Schmideder et al (2020) [31]. That cultivation in pellet form is less problematic for gas-liquid mass transfer and liquid mixing due to the lower viscosity of the fermentation broth has been reported in other studies [25,32,33].…”

Something old, something new: challenges and developments in Aspergillus niger biotechnology

“…The key advantage of this novel μCT technique is thus the possibility to determine the exact inner structure of intact fungal pellets and to calculate the effective diffusion factor inside an A. niger pellet in relation to the hyphal fraction [84]. Remarkably, it was shown that the correlation between effective diffusion factor and hyphal fraction in fungal pellets follows a universal law, which is independent of micromorphological features like hyphal diameter, branching angle or interval and growth angle [85]. With this new tool, it is conceivable to calculate the actual nutrient or oxygen gradient within a pellet in a foreseeable future.…”