Vesicle transport and growth dynamics in Aspergillus niger: Microscale modeling of secretory vesicle flow and centerline extraction from confocal fluorescent data

In this paper, we present a mathematical model to describe filamentous fungal growth based on intracellular secretory vesicles (SVs), which transport cell wall components to the hyphal tip. Vesicular transport inside elongating hyphae is modeled as an advection–diffusion–reaction equation with a moving boundary, transformed into fixed coordinates, and discretized using a high‐order weighted essentially nonoscillatory discretization scheme. The model describes the production and the consumption of SVs with kinetic functions. Simulations are subsequently compared against distributions of SVs visualized by enhanced green fluorescent protein in young Aspergillus niger hyphae after germination. Intensity profile data are obtained using an algorithm scripted in ImageJ that extracts mean intensity distributions from 3D time‐lapse confocal measurement data. Simulated length growth is in good agreement with the experimental data. Our simulations further show that a decrease of effective vesicle transport velocity towards the tip can explain the observed tip accumulation of SVs.DFG, 273937032, SPP 1934: Dispersitäts-, Struktur- und Phasenänderungen von Proteinen und biologischen Agglomeraten in biotechnologischen ProzessenTU Berlin, Open-Access-Mittel – 202

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

Filamentous fungal cell factories are efficient producers of platform chemicals, proteins, enzymes and natural products. Stirred-tank bioreactors up to a scale of several hundred m³ are commonly used for their cultivation. Fungal hyphae self-assemble into various cellular macromorphologies ranging from dispersed mycelia, loose clumps, to compact pellets. Development of these macromorphologies is so far unpredictable but strongly impacts productivities of fungal bioprocesses. Depending on the strain and the desired product, the morphological forms vary, but no strain- or product-related correlations currently exist to improve process understanding of fungal production systems. However, novel genomic, genetic, metabolic, imaging and modelling tools have recently been established that will provide fundamental new insights into filamentous fungal growth and how it is balanced with product formation. In this primer, these tools will be highlighted and their revolutionary impact on rational morphology engineering and bioprocess control will be discussed.DFG, 315305620, Untersuchung des Einflusses von Scherkräften auf das morphogenetische Gennetzwerk, die Zellintegrität, mikroskopische und makroskopische Morphologie von Aspergillus niger sowie Bildungsraten intra- und extrazellulärer ProdukteDFG, 315384307, Verallgemeinerte morphologische Modellierung aggregierender, filamentöser MikroorganismenDFG, 315457657, Untersuchung und Modellierung der mechanischen und Oberflächen-induzierten Beanspruchung von Pellets filamentöser Mikroorganismen am Beispiel von Lechevalieria aerocolonigenesTU Berlin, Open-Access-Mittel – 202