Integrated Approaches for Assessment of Cellular Performance in Industrially Relevant Filamentous Fungi

Abstract

The performance of filamentous fungi in submerged cultivation determines their suitability for large-scale industrial biotechnology processes and is the result of complex interplay between the physical and chemical parameters of the process and the cellular biology of the fungi. Filamentous fungi have a natural ability to degrade complex substrates through secretion of a large number of diverse enzymes and to produce a number of metabolites that inhibit or prevent the growth of other species in the surroundings. These features have been exploited by industry, resulting in multi-billion dollar processes for producing enzymes and metabolites of value. However, the wealth of diversity of these species is still not fully represented in large-scale bioprocesses, and thus advancement from discovery to application is one of the challenges for modern biotechnology. Acceleration of the process can be achieved through integrated approaches for assessing cellular performance (quantitative physiology), genetic modification of strains (metabolic engineering), and omics analyses and modeling (systems biology). In this review, we evaluate stateof-the-art of filamentous fungal applications in industrial biotechnology , focusing on physiological aspects of the fungi that provide the basis of their cellular performance. We also discuss the advancement of systems biology approaches and how the establishment of these tools for fungal research has begun to reveal the possibilities for further exploitation of these organisms. Increased future focus on multicellular physiology and relevant assays will lead to fungal cells and processes that are customizable to a greater degree, finally allowing the full potential of these complex organisms and their product diversity to unfold.

Production of cellulolytic enzymes from ascomycetes: Comparison of solid state and submerged fermentation

“…One of the major challenges for production of enzymes in SmF is the multicellular nature of filamentous fungi, which affects the reproducibility of cultivations [111]. Reproducibility of submerged cultivations can be highly affected by the mass transfer of oxygen.…”

A community-driven reconstruction of the Aspergillus niger metabolic network

“…Aspergillus niger described in 1867 by Van Tiegham, sparked considerable interest due to the observation of citric acid overproduction in the beginning of the last century [ 9 ]. Besides being an industrial work-horse in citric acid production, A. niger and its close relatives are also widely used hosts for enzyme production [ 10 , 11 ]. Owing to the commercial interest in A. niger and its metabolic flexibility with respect to utilizable substrates, there has been sustained research to elucidate the metabolism of this organism.…”

The Taming of the Shrew - Controlling the Morphology of Filamentous Eukaryotic and Prokaryotic Microorganisms

“…Very high titres of hydrolytic enzymes, such as amylases and proteases, can be produced by these species; for example, titres of up to 30 g/L of glucoamylase can be achieved by A. niger [8], and industrial strains of T. reesei have been shown to secrete 40 g/L of cellulases into the cultivation medium [9]. Driven by advances in equipment and analytics, laboratory-scale fungal cultivation techniques have improved substantially over the last 10-15 years, enabling the completion of reproducible and repeatable bioreactor experiments [10].…”

“…Several recent reviews have focused on filamentous fungi, covering morphology and productivity [53,54,[57][58][59][60], process design [61] and molecular characteristics [3,10,62]. Figure 1 highlights the most frequently cited key publications on bioprocesses involving filamentous microorganisms over the last 65 years.…”