Effects and interactions of metal oxides in microparticle‐enhanced cultivation of filamentous microorganisms

Abstract

Filamentous microorganisms are used as molecular factories in industrial biotechnology. In 2007, a new approach to improve productivity in submerged cultivation was introduced: microparticle-enhanced cultivation (MPEC). Since then, numerous studies have investigated the influence of microparticles on the cultivation. Most studies considered MPEC a morphology engineering approach, in which altered morphology results in increased productivity. But sometimes similar morphological changes lead to decreased productivity, suggesting that this hypothesis is not a sufficient explanation for the effects of microparticles. Effects of surface chemistry on particles were paid little attention, as particles were often considered chemically-inert and bioinert. However, metal oxide particles strongly interact with their environment. This review links morphological, physical, and chemical properties of microparticles with effects on culture broth, filamentous morphology, and molecular biology.More precisely, surface chemistry effects of metal oxide particles lead to ion leaching, adsorption of enzymes, and generation of reactive oxygen species.Therefore, microparticles interfere with gene regulation, metabolism, and activity of enzymes. To enhance the understanding of microparticle-based morphology engineering, further interactions between particles and cells are elaborated. The presented description of phenomena occurring in MPEC eases the targeted choice of microparticles, and thus, contributes to improving the productivity of microbial cultivation technology.

From spores to fungal pellets: A new high‐throughput image analysis highlights the structural development of Aspergillus niger

“…Different strategies have thus been developed to increase the productivity of bioprocesses by altering fungal macromorphologies. Most of them focus on the variation of the cultivation conditions, including medium composition, pH and osmolality of the medium, spore inoculum concentration, viability/vitality of the inoculum, bioreactor geometry, shear stress, aeration rate, temperature, and the addition of microparticles to name but a few (Böl et al, 2021; Driouch et al, 2010; Kaup et al, 2008; Laible et al, 2021; Papagianni, 2004; Wucherpfennig et al, 2010, 2011). Genetic factors and intracellular processes that affect or even control spore germination, hyphal growth, and eventually pellet formation can be grouped into cytoskeletal networks, exocytosis, endocytosis, cell membrane, and cell wall biogenesis.…”

Co-cultivation of filamentous microorganisms in the presence of aluminum oxide microparticles

“…The differences in medium composition (e.g., the presence or absence of phenylacetic acid) were responsible for the medium-dependent effectiveness of AO, but further studies are required to uncover the details of this behavior. As the interactions between the microparticles, the growth medium and cultivated cells are intrinsically complex and occur at multiple levels, elucidating the molecular mechanisms associated with the medium-dependent impact of microparticles on the production of secondary metabolites is undoubtedly a challenging task (Laible et al 2021 ).…”

“…Briefly, the basic idea of MPEC is to enhance the performance of production strains by affecting their morphological phenotypes through the addition of microparticles, e.g., talc or aluminum oxide (AO), to the medium. While the effectiveness of MPEC in the context of bioprocess development has been proven (Böl et al 2021 ; Karahalil et al 2019 ; Meyer et al 2021 ; Walisko et al 2015 ), the complexity of physical and chemical interactions between the microparticles and the cultivated cells is still under intensive investigation (this topic was recently reviewed by Laible et al 2021 ). Since the productivity of filamentous microorganisms is known to depend on the exhibited morphological forms (i.e., dispersed mycelia, clumps or the aggregated biomass known as “pellets”) and their characteristics (i.e., size, shape and structure), controlling the morphology in submerged cultivations is of key importance in the context of developing economically feasible biomanufacturing processes (Veiter et al 2018 ; Wucherpfennig et al 2010 ).…”

Morphology engineering for novel antibiotics: Effect of glass microparticles and soy lecithin on rebeccamycin production and cellular morphology of filamentous actinomycete Lentzea aerocolonigenes

“…Additionally, other filamentous fungi and one filamentous bacterium were also proven to be positively affected in the same study ( Kaup et al, 2008 ). As of this date, multiple successful examples of MPEC have been published for filamentous fungi and bacteria, as summarized by Laible et al (2021) . Generally, MPEC is associated with a multi-layered effect on mycelial biomass.…”

“…So far, the most commonly used materials for MPEC are talc (Mg 3 [(OH) 2 |Si 4 O 10 ]), aluminum oxide (Al 2 O 3 ), and, more scarcely, titanate (TiO 2 ). However, usually little information is provided regarding these materials beyond particle size, although the properties of these metal oxide species differ fundamentally regarding morphological characteristics and physiochemical properties ( Laible et al, 2021 ). Thus, a microparticle system with more consistent particle properties is demanded to better control and modulate the challenging filamentous cultures.…”