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Development of cultivation strategies for friulimicin production in Actinoplanes friuliensis

Paper ID Volume ID Publish Year Pages File Format Full-Text
22939 43401 2015 8 PDF Available
Title
Development of cultivation strategies for friulimicin production in Actinoplanes friuliensis
Abstract

•A chemically defined medium for characterization of friulimicin biosynthesis.•Phosphate and ammonium inhibited friulimicin biosynthesis.•Perfusion processes enhanced volumetric productivity compared to fed-batch processes.•Flux analyses revealed high energetic efficiency of growth.•A large portion of the supplied amino acids is used as supplemental carbon source.

Actinoplanes friuliensis is a rare actinomycete which produces the highly potent lipopeptide antibiotic friulimicin. This lipopeptide antibiotic is active against a broad range of multi-resistant gram-positive bacteria such as methicillin-resistant Enterococcus sp. and Staphylococcus aureus (MRE, MRSA) strains.Antibiotic biosynthesis and regulation in actinomycetes is very complex. In order to study the biosynthesis of these species and to develop efficient production processes, standardized cultivation conditions are a prerequisite. For this reason a chemically defined production medium for A. friuliensis was developed. With this chemically defined medium it was possible to analyze the influence of medium components on growth and antibiotic biosynthesis.These findings were used to develop process strategies for friulimicin production. The focus of the project presented here was to develop cultivation strategies which included fed-batch and continuous cultivation processes. In fed-batch processes, volumetric productivities for friulimicin of 1–2 mg/l h were achieved. In a perfusion process, a very simple cell retention system, which works via sedimentation of the mycelial cell pellets, was used. With this system, stable continuous cultivations with cell retention were dependent on the dilution rate. With a dilution rate of 0.05 h−1, cell retention worked well and volumetric productivity of friulimicin was enhanced to 3–5 mg/l h. With a higher dilution rate of 0.1 h−1, friulimicin production ceased because cell retention was not possible any longer with this simple cell retention system. In order to support process development, cultivation data were used to characterize metabolic fluxes in the developed friulimicin production processes.

Keywords
Lipopeptide antibiotic; Chemically defined medium; Fed-batch cultivation; Continuous cultivation; Metabolic flux analysis
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Development of cultivation strategies for friulimicin production in Actinoplanes friuliensis
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 195, 10 February 2015, Pages 52–59
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
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Full-text PDF Download
Online Support
Any Questions? feel free to contact us