Fermentation broth of Bacillus thuringiensis as a source of precursors for production of nikkomycins

Vecht-Lifshitz, Susan E.; Braun, Sergei

doi:10.1111/j.1472-765x.1989.tb00296.x

Cited by 9 publications

(2 citation statements)

References 9 publications

(8 reference statements)

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“…Specifically uracil increased Nk Z and suppressed Nk X only when glucose was absent from the medium. The use of yeast RNA, Escherichia coli powder and spent broth from Bacillus thuringiensis, all believed to be cheap sources of nucleosides and amino acids, stimulated overall nikkomycin yields although purity was not mentioned (Vecht-Lifshitz and Braun, 1989). In a different system, while L-lysine at 5-20 g/L increased production of desferrioxamine E, the addition of Lthreonine without L-lysine decreased desferrioxamine E by 80% and increased desferrioxamine D 2 by up to 270% (Meiwes et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Secondary metabolite scale‐up to minimize homolog impurity levels

Junker¹,

Reddy²,

Olewinski³

et al. 1998

Biotechnol. Bioeng.

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A mutant strain of Streptomyces hygroscopicus was found to produce up to 9.0 units/L of an immunoregulant precursor, immunomycin, with up to 3.5% of a lower homolog impurity under either dual fed-batch or batch conditions. Glycerol and valine were key nutrients influencing productivity and impurity levels. Soybean oil was successfully substituted for glycerol as a carbon source to minimize shot additions to batch culture. The remainder of the production medium was composed largely of defined components with the exception of yeast extract.Valine limitation increased lower homolog formation while decreasing higher homolog formation; excess valine decreased lower homolog formation below 2-3% while increasing higher homolog formation. Higher homolog formation in the presence of valine seemed to be slower than lower homolog formation in the absence of valine. Valine was believed to be the major butyrate precursor; consequently its availability influenced the impurity profile. A preliminary cost analysis suggests that elimination of added valine from the cultivation and replacement of glycerol with soybean oil can result in a 6.6-fold reduction in media costs relative to the original fed-batch process.

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Section: Introductionmentioning

confidence: 99%

Secondary metabolite scale‐up to minimize homolog impurity levels

Junker¹,

Reddy²,

Olewinski³

et al. 1998

Biotechnol. Bioeng.

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“…No nikkomycin X was observed in the fermentation broth from the ΔNikQ 25-2 strain, whereas the wild-type ATCC strain made both nikkomycin Z and nikkomycin X. Rational screening for strain improvement has proven useful for antibiotic production. , The toxic analogue, 5-fluorouracil, was chosen for the first selection since the literature reports that feeding uracil resulted in improved nikkomycin Z production and selection of 5-fluorouracil resistant mutants also improved nikkomycin Z production . From the first round of mutagenesis an improved strain Streptomyces tendae ΔNikQ 25-2 UMN01E7, was obtained.…”

Section: Resultsmentioning

confidence: 99%

A Practical and Scalable Manufacturing Process for an Antifungal Agent, Nikkomycin Z

Stenland

Lis

Schendel

et al. 2013

Org. Process Res. Dev.

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A scalable and reliable manufacturing process for Nikkomycin Z HCl on a 170 g scale has been developed and optimized. The process is characterized by a 2.3 g/L fermentation yield, 79% purification yield, and >98% relative purity of the final product. This method is suitable for further scale up and cGMP production. The Streptomyces tendae ΔNikQ strain developed during the course of this study is superior to any previously reported strain in terms of higher yield and purity of Nikkomycin Z.

show abstract

Secondary metabolite scale-up to minimize homolog impurity levels

Junker

Reddy

Olewinski

et al. 1998

Biotechnol. Bioeng.

View full text Add to dashboard Cite

A mutant strain of Streptomyces hygroscopicus was found to produce up to 9.0 units/L of an immunoregulant precursor, immunomycin, with up to 3.5% of a lower homolog impurity under either dual fed‐batch or batch conditions. Glycerol and valine were key nutrients influencing productivity and impurity levels. Soybean oil was successfully substituted for glycerol as a carbon source to minimize shot additions to batch culture. The remainder of the production medium was composed largely of defined components with the exception of yeast extract. Valine limitation increased lower homolog formation while decreasing higher homolog formation; excess valine decreased lower homolog formation below 2–3% while increasing higher homolog formation. Higher homolog formation in the presence of valine seemed to be slower than lower homolog formation in the absence of valine. Valine was believed to be the major butyrate precursor; consequently its availability influenced the impurity profile. A preliminary cost analysis suggests that elimination of added valine from the cultivation and replacement of glycerol with soybean oil can result in a 6.6‐fold reduction in media costs relative to the original fed‐batch process. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 59:595–604, 1998.

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Fermentation broth of Bacillus thuringiensis as a source of precursors for production of nikkomycins

Cited by 9 publications

References 9 publications

Secondary metabolite scale‐up to minimize homolog impurity levels

Secondary metabolite scale‐up to minimize homolog impurity levels

A Practical and Scalable Manufacturing Process for an Antifungal Agent, Nikkomycin Z

Secondary metabolite scale-up to minimize homolog impurity levels

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