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

In this work, a robust brefeldin A-synthesizing fungus, Eupenicillium brefeldianum ZJB082702, was bred from a Murraya paniculata endophytic fungus E. brefeldianum A1163. Using one-factor-at-a-time experimental design, optimization of media composition for E. brefeldianum ZJB082702 fermenting brefeldin A was conducted. Outcomes indicated that mixed carbon source and mixed nitrogen source were of c ritical importance to brefeldin A fermentation. After 6 d culture in the optimized fermentation media, composed of (g l−1) 13.33 starch, 26.67 glucose, 1.0 yeast extract powder, 1.0 corn steep liquor, 0.5 soybean meal, 0.75 NaNO3, 2.5 malt extract, 6.0 CaCO3, 3.0 MgSO4, 4.0 KH2PO4, 1.0 × 10−2 CuSO4, brefeldin A yield peaked at 1304.7 mg l−1, 648.2 mg l−1 in 500 ml baffled flask and 15 l stirred fermentor respectively, formed as a growth associated type of secondary metabolite based on fermentation profile analysis.

► A brefeldin A overproducing fungus, E. brefeldianum ZJB082702, was bred. ► Mixed carbon, nitrogen sources were critical to brefeldin A synthesis. ► Brefeldin A is synthesized by E. brefeldianum in a growth associated manner. ► Six-day culture in baffled flasks gave a peak brefeldin A yield of 1304.7 mg l−1. ► Brefeldin A titer peaked at 648.2 mg l−1 in 15 l stirred fermentor.