Production of brefeldin-A

Abstract

Fermentatiion conditions are described for the production of the antitumor antibiotic 7-(S)-brefeldin-A (brefeldin-A) in liquid culture by Eupenicillium brefeldianum, (B. Dodge) Stolk and Scott, ATCC 58665. An analytical hplc method was developed which allowed rapid quantitation of the compound during fermentation. A kilogram of brefeldin-A was isolated from a fermentation at the 6800-liter scale.

Fungal Polyketide Synthase Product Chain-Length Control by Partnering Thiohydrolase

“…For BFA production and for mRNA extraction, the strain was grown in liquid MEM media at RT with 250 rpm shaking. 42 Saccharomyces cerevisiae BJ5464 was used for protein expression of bref- PKS and subsequent in vivo production of 3 – 6 . This strain was maintained and cultured in YPD, while the transformants carrying the recombinant plasmids were grown in synthetic defined dropout media with appropriate supplements.…”

cis-Golgi proteins accumulate near the ER exit sites and act as the scaffold for Golgi regeneration after brefeldin A treatment in tobacco BY-2 cells

“…Brefeldin A (BFA), an antibiotic compound produced by fungi, is known as a potent inhibitor of guanine nucleotide exchange factors (GEFs) for ARF GTPases (McCloud et al ., 1995; Chardin and McCormick, 1999). ARF1 regulates formation of COPI-coated vesicles from the Golgi, which mediate retrograde transport from the Golgi to the ER (Donaldson et al ., 2005).…”

Development of macrolide lactone antibiotic brefeldin A fermentation process with Eupenicillium brefeldianum ZJB082702

“…These plates were cultivated in an incubator at 28 C for 1 week. Isolates were grown in a maltose medium, composed of (g l À1 ): maltose 30.0, malt extract 1.5, yeast exact 2.5, KH 2 PO 4 2.0, MgSO 4 $7H 2 O 2.0, CaCO 3 4.0, which was formulated by referring to the fermentation media published (22,29). Single colonies were transferred to PDA media, grown at 28 C till visible colonies emerged.…”

“…Phyllosticta medicaginis fermentation gave a maximal brefeldin A titer of approximately 300 mg l À1 as described previously (Howard, C.C., Johnstone, R.A.W., and Entwistle, I.D., US Patent, 3,896,002,1975). Culture with Eupenicillium brefeldianum ATCC 58665 produced a maximal titer of 169 mg l À1 on a 6800 l scale (22). These fermentations however suffered from low productivity, contributing to its extraordinarily high price.…”