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Bioengineering 2018, 5(2), 42; https://doi.org/10.3390/bioengineering5020042

Large Scale Production and Downstream Processing of Labyrinthopeptins from the Actinobacterium Actinomadura namibiensis

1
Department Microbial Drugs, Helmholtz Centre for Infection Research GmbH, Inhoffenstraße 7, 38124 Braunschweig, Germany
2
German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, 38124 Braunschweig, Germany
3
Toyama Prefectural University, 5180 Kurokawa Imizu-shi, Toyama 939-0398, Japan
*
Authors to whom correspondence should be addressed.
Received: 4 May 2018 / Revised: 31 May 2018 / Accepted: 2 June 2018 / Published: 5 June 2018
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Abstract

A method was established for the production of 1.2-fold and 4.2-fold increased amounts of the antiviral and central nervous system-active lantipeptides, labyrinthopeptins A1 and A2, respectively, isolated from the actinobacterium Actinomadura namibiensis, to enable production in gram scale. We then performed in vivo characterization of this promising compound class. The labyrinthopeptins A1 and A2 have similar chemical structures and physical properties but differ drastically in their bioactivities. Therefore, large quantities of highly pure material are required for pharmacological studies. An effective methodology was established for the first time for their production in bioreactors, their separation involving gel permeation chromatography on LH20 material, followed by reversed phase-high performance liquid chromatography. With an optimized methodology, 580 mg of labyrinthopeptin A1 and 510 mg of labyrinthopeptin A2 were quantitatively isolated with recovery rates of 72.5% and 42.3% from 7.5 L of culture broth, respectively. However, the fermentation that had already resulted in maximum yields of over 100 mg/L of both target molecules after 300 h in a 10-L scale bioreactor, still requires further optimisation. View Full-Text
Keywords: anti-viral agents; bioprocess; central nervous system; lantibiotics; optimization production; reversed phase-high performance liquid chromatography; scale-up anti-viral agents; bioprocess; central nervous system; lantibiotics; optimization production; reversed phase-high performance liquid chromatography; scale-up
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Rupcic, Z.; Hüttel, S.; Bernecker, S.; Kanaki, S.; Stadler, M. Large Scale Production and Downstream Processing of Labyrinthopeptins from the Actinobacterium Actinomadura namibiensis. Bioengineering 2018, 5, 42.

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