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Production of Calcaride A by Calcarisporium sp. in Shaken Flasks and Stirred Bioreactors

Increased interest in marine resources has led to increased screening of marine fungi for novel bioactive compounds and considerable effort is being invested in discovering these metabolites. For compound discovery, small-scale cultures are adequate, but agitated bioreactors are desirable for larger...

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Autores principales: Tamminen, Anu, Wang, Yanming, Wiebe, Marilyn G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515605/
https://www.ncbi.nlm.nih.gov/pubmed/26114617
http://dx.doi.org/10.3390/md13073992
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author Tamminen, Anu
Wang, Yanming
Wiebe, Marilyn G.
author_facet Tamminen, Anu
Wang, Yanming
Wiebe, Marilyn G.
author_sort Tamminen, Anu
collection PubMed
description Increased interest in marine resources has led to increased screening of marine fungi for novel bioactive compounds and considerable effort is being invested in discovering these metabolites. For compound discovery, small-scale cultures are adequate, but agitated bioreactors are desirable for larger-scale production. Calcarisporium sp. KF525 has recently been described to produce calcaride A, a cyclic polyester with antibiotic activity, in agitated flasks. Here, we describe improvements in the production of calcaride A in both flasks (13-fold improvement) and stirred bioreactors (200-fold improvement). Production of calcaride A in bioreactors was initially substantially lower than in shaken flasks. The cultivation pH (reduced from 6.8 to <5.4), carbon source (sucrose replacing glucose), C/N ratio and nature of mycelial growth (pellets or filaments) were important in improving calcaride A production. Up to 4.5 mg·g(−1) biomass (85 mg·L(−1)) calcaride A were produced in the bioreactor, which was only slightly less than in shaken flasks (14 mg·g(−1), 100 mg·L(−1)). The results demonstrate that a scalable process for calcaride A production could be developed using an iterative approach with flasks and bioreactors.
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spelling pubmed-45156052015-07-28 Production of Calcaride A by Calcarisporium sp. in Shaken Flasks and Stirred Bioreactors Tamminen, Anu Wang, Yanming Wiebe, Marilyn G. Mar Drugs Article Increased interest in marine resources has led to increased screening of marine fungi for novel bioactive compounds and considerable effort is being invested in discovering these metabolites. For compound discovery, small-scale cultures are adequate, but agitated bioreactors are desirable for larger-scale production. Calcarisporium sp. KF525 has recently been described to produce calcaride A, a cyclic polyester with antibiotic activity, in agitated flasks. Here, we describe improvements in the production of calcaride A in both flasks (13-fold improvement) and stirred bioreactors (200-fold improvement). Production of calcaride A in bioreactors was initially substantially lower than in shaken flasks. The cultivation pH (reduced from 6.8 to <5.4), carbon source (sucrose replacing glucose), C/N ratio and nature of mycelial growth (pellets or filaments) were important in improving calcaride A production. Up to 4.5 mg·g(−1) biomass (85 mg·L(−1)) calcaride A were produced in the bioreactor, which was only slightly less than in shaken flasks (14 mg·g(−1), 100 mg·L(−1)). The results demonstrate that a scalable process for calcaride A production could be developed using an iterative approach with flasks and bioreactors. MDPI 2015-06-24 /pmc/articles/PMC4515605/ /pubmed/26114617 http://dx.doi.org/10.3390/md13073992 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tamminen, Anu
Wang, Yanming
Wiebe, Marilyn G.
Production of Calcaride A by Calcarisporium sp. in Shaken Flasks and Stirred Bioreactors
title Production of Calcaride A by Calcarisporium sp. in Shaken Flasks and Stirred Bioreactors
title_full Production of Calcaride A by Calcarisporium sp. in Shaken Flasks and Stirred Bioreactors
title_fullStr Production of Calcaride A by Calcarisporium sp. in Shaken Flasks and Stirred Bioreactors
title_full_unstemmed Production of Calcaride A by Calcarisporium sp. in Shaken Flasks and Stirred Bioreactors
title_short Production of Calcaride A by Calcarisporium sp. in Shaken Flasks and Stirred Bioreactors
title_sort production of calcaride a by calcarisporium sp. in shaken flasks and stirred bioreactors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515605/
https://www.ncbi.nlm.nih.gov/pubmed/26114617
http://dx.doi.org/10.3390/md13073992
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