Effects of amino acid and trace element supplementation on pneumocandin production by Glarea lozoyensis: Impact on titer, analogue levels, and the identification of new analogues of pneumocandin B0

Abstract

Addition of the amino acids threonine, serine, proline, and fermentations of the fungus Glarea lozoyensis influenced both the pneumocandin titer and the spectrum of analogues produced. Addition of threonine or serine altered the levels of the "serine analogues" of pneumocandins B0 and B5 and allowed for their isolation and identification. Proline supplementation resulted in a dose-dependent increase in the levels of pneumocandins B0 and E0, whereas pneumocandins C0 and D0 decreased as a function of proline level. Moreover, proline supplementation resulted in an overall increase in the synthesis of both trans-3 and trans-4-hydroxyproline while maintaining a low trans-4-hydroxyproline to trans-3-hydroxyproline ratio compare to the unsupplemented culture. Pneumocandin production and the synthesis of hydroxyprolines was also affected by addition of the proline-related amino acid arginine but not by the addition of glutamine or ornithine. Zinc, cobalt, copper, and nickle, trace elements that are known to inhibit α-ketoglutarate-dependent dioxygenases, affected the pneumocandin B0 titer and altered the levels of pnemocandins B1, B2, B5, B6, and E0, analogues that process altered proline, ornithine, and tyrosine hydroxylation patterns.