During the past five years, the number of single‐use bioreactors used in biopharmaceutical research and production has increased tremendously. This increase has been particularly associated with mammalian cell culture processes from small‐ to medium‐scale volumes. Even though nowadays customers can choose from a multitude of 2nd and 3rd generation single‐use bioreactors, ranging from mL‐ up to m3‐scale, there is a lack of knowledge of their engineering parameters. Different approaches have been applied to characterization investigations, resulting in an inability to compare different single‐use bioreactors with each other and their reusable counterparts, creating an obstacle to a systematic approach to scaling‐up the process. This article describes parametric, experimental and computer‐based numeric methods for biochemical engineering characterization of single‐use bioreactors, which have already been used successfully for the characterization of their reusable counterparts. For the first time, these methods have been evaluated in terms of their practical application.
Halogenated organic compounds constitute one of the largest and most diverse groups of chemicals in the environment. Many of these compounds are toxic, persistent and, as a result of their often limited biodegradability, tend to bioaccumulate in the environment. Dibromoneopentyl glycol (DBNPG) and tribromoneopentyl alcohol (TBNPA) are brominated flame retardants commonly used as additives during the manufacture of plastic polymers and as chemical intermediates in the synthesis of other flame retardants. Both are classified as not readily biodegradable. In this paper, we demonstrate the biodegradation of both DBNPG and TBNPA by a common bacterial consortium under aerobic conditions in enrichment cultures containing yeast extract. DBNPG and TBNPA biodegradation is accompanied by a release of bromide into the medium, due to a biological debromination reaction. Molecular analysis of the clone library PCR amplified 16S rRNA gene was used to characterize the bacterial consortium involved in the biodegradation.
The antibiotic and fungicidal deuteromycete Mollisia caesia Sacc. was cultivated on a large scale. Mollisin (1; = 8-(dichloroacetyl)-5-hydroxy-2,7-dimethylnaphthalene-1,4-dione) and two new tri- and tetrahalogenated metabolites, mollisin A (2) and mollisin B (3) were isolated from M. caesia. The formation of 2 and 3 indicates that the biosynthesis of these compounds starts from a C(16) polyketide (Scheme). Mollisin (1) shows strong fungicidal activities against Sclerophoma pityophila (Corda) v. Höhn and Heterobasidion annosum (Fr.) Bref., which is one of the most-destructive basidiomycetes in coniferous forests. The metabolites 1-3 possess interesting pharmacological activities in assays in search of anti-inflammatory and antiproliferative drugs.
The main goal of the Bioprocess Technology working group is to overcome existing knowledge deficits in the bioprocess characterization of single‐use bioreactors. The required methods have been investigated extensively, evaluated for their suitability for certain single‐use bioreactors, and summarized into a basic structure in the so‐called conceptual matrix. Development of standard operating procedures for the methods selected as well as their verification in interlaboratory tests guarantee that in the future a spectrum of unified and validated methods can be used to compare different bioreactor types objectively.
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