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Main Title: Rocking Aspergillus: morphology-controlled cultivation of Aspergillus niger in a wave-mixed bioreactor for the production of secondary metabolites
Author(s): Kurt, Tutku
Marbà-Ardébol, Anna-Maria
Turan, Zeynep
Neubauer, Peter
Junne, Stefan
Meyer, Vera
Type: Article
Language Code: en
Abstract: Background Filamentous fungi including Aspergillus niger are cell factories for the production of organic acids, proteins and bioactive compounds. Traditionally, stirred-tank reactors (STRs) are used to cultivate them under highly reproducible conditions ensuring optimum oxygen uptake and high growth rates. However, agitation via mechanical stirring causes high shear forces, thus affecting fungal physiology and macromorphologies. Two-dimensional rocking-motion wave-mixed bioreactor cultivations could offer a viable alternative to fungal cultivations in STRs, as comparable gas mass transfer is generally achievable while deploying lower friction and shear forces. The aim of this study was thus to investigate for the first time the consequences of wave-mixed cultivations on the growth, macromorphology and product formation of A. niger. Results We investigated the impact of hydrodynamic conditions on A. niger cultivated at a 5 L scale in a disposable two-dimensional rocking motion bioreactor (CELL-tainer®) and a BioFlo STR (New Brunswick®), respectively. Two different A. niger strains were analysed, which produce heterologously the commercial drug enniatin B. Both strains expressed the esyn1 gene that encodes a non-ribosomal peptide synthetase ESYN under control of the inducible Tet-on system, but differed in their dependence on feeding with the precursors d-2-hydroxyvaleric acid and l-valine. Cultivations of A. niger in the CELL-tainer resulted in the formation of large pellets, which were heterogeneous in size (diameter 300–800 μm) and not observed during STR cultivations. When talcum microparticles were added, it was possible to obtain a reduced pellet size and to control pellet heterogeneity (diameter 50–150 μm). No foam formation was observed under wave-mixed cultivation conditions, which made the addition of antifoam agents needless. Overall, enniatin B titres of about 1.5–2.3 g L−1 were achieved in the CELL-tainer® system, which is about 30–50% of the titres achieved under STR conditions. Conclusions This is the first report studying the potential use of single-use wave-mixed reactor systems for the cultivation of A. niger. Although final enniatin yields are not competitive yet with titres achieved under STR conditions, wave-mixed cultivations open up new avenues for the cultivation of shear-sensitive mutant strains as well as high cell-density cultivations.
Issue Date: 21-Aug-2018
Date Available: 4-Sep-2018
DDC Class: 570 Biowissenschaften; Biologie
610 Medizin und Gesundheit
Subject(s): single-use wave-mixed bioreactor
Aspergillus niger
heterologous gene expression
talcum microparticle
tet-on system
Sponsor/Funder: DFG, TH 662/19-1, Open Access Publizieren 2017 - 2018 / Technische Universität Berlin
Journal Title: Microbial Cell Factories
Publisher: Biomed Central
Publisher Place: London
Volume: 17
Issue: 1
Article Number: 128
Publisher DOI: 10.1186/s12934-018-0975-y
ISSN: 1475-2859
Appears in Collections:FG Angewandte und Molekulare Mikrobiologie » Publications

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