Challenges of influencing cellular morphology by morphology engineering techniques and mechanical induced stress on filamentous pellet systems—A critical review

Abstract

Filamentous microorganisms are main producers of organic acids, enzymes, and pharmaceutical agents such as antibiotics and other active pharmaceutical ingredients. With their complex cell morphology, ranging from dispersed mycelia to dense pellets, the cultivation is challenging. In recent years, various techniques for tailor‐made cell morphologies of filamentous microorganisms have been developed to increase product formation and have been summarised under the term morphology engineering. These techniques, namely microparticle‐enhanced cultivation, macroparticle‐enhanced cultivation, and alteration of the osmolality of the culture medium by addition of inorganic salts, the salt‐enhanced cultivation, are presented and discussed in this review. These techniques have already proven to be useful and now await further proof‐of‐concept. Furthermore, the mechanical behaviour of individual pellets is of special interest for a general understanding of pellet mechanics and the productivity of biotechnological processes with filamentous microorganisms. Correlating them with substrate uptake and finally with productivity would be a breakthrough not to be underestimated for the comprehensive characterisation of filamentous systems. So far, this research field is under‐represented. First results on filamentous pellet mechanics are discussed and important future aspects, which the filamentous expert community should deal with, will be presented and critically discussed.

Microparticles enhance the formation of seven major classes of natural products in native and metabolically engineered actinobacteria through accelerated morphological development

“…Although the optimum talc level differed between strains and products, a concentration of 10 g L −1 always revealed a significant effect. Altogether, microparticle‐enhanced cultivation provides a valuable concept for natural product research in actinobacteria, complementing efforts to streamline eukaryotic filamentous fungi (Böl et al, 2020; Veiter et al, 2018).…”

Enhanced Oxytetracycline Production by Streptomyces rimosus in Submerged Co-Cultures with Streptomyces noursei

“…When investigating the production of secondary metabolites in relation to morphological development, the correlations between metabolite levels and morphological characteristics are always sought. One of the behaviors typically observed in past studies involved the decrease in pellet size through morphological engineering, leading in turn to the increase in target product levels (recently reviewed in [ 23 ]). Here, when the morphological results obtained for the “ S. rimosus versus S. noursei ” co-cultivation were compared with the data gathered for other (less effective) co-cultures, there was no evidence that the morphology could be a key factor determining the effectiveness of this variant.…”

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

“…Therefore, various strategies to generate tailor-made fungal cell morphologies have been pursued in the last decade. They include genetic approaches as well as micro-, macro-particle and salt-enhanced cultivation techniques and are summarised under the term morphology engineering [ 3 , 14 ].…”

“…In order to bridge the scales between the pellets and the bioreactor, turbulent flow models must be linked. Pellet-specific and morphology-dependent product formation rate expressions for these interactions have to be derived, calibrated and validated [ 14 ]. Also, rheo-morphological parameter correlations are challenging due to the large variability of mycelial structures in submerged cultures.…”