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

  • L A Petersen
  • D L Hughes
  • R Hughes
  • L DiMichele
  • P Salmon
  • N Connors

DOI: 10.1038/sj.jim.7000115

Cite this article as:
Petersen, L., Hughes, D., Hughes, R. et al. J Ind Microbiol Biotech (2001) 26: 216. doi:10.1038/sj.jim.7000115

Addition of the amino acids threonine, serine, proline, and arginine to 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 compared 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 nickel, trace elements that are known to inhibit α-ketoglutarate-dependent dioxygenases, affected the pneumocandin B0 titer and altered the levels of pneumocandins B1, B2, B5, B6, and E0, analogues that possess altered proline, ornithine, and tyrosine hydroxylation patterns. Journal of Industrial Microbiology & Biotechnology (2001) 26, 216–221.

Keywords: pneumocandin; antifungal; Glarea lozoyensis; fermentation; hydroxyproline; nonribosomal peptide synthetase 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Society for Industrial Microbiology 2001

Authors and Affiliations

  • L A Petersen
    • 1
  • D L Hughes
    • 2
  • R Hughes
    • 1
  • L DiMichele
    • 2
  • P Salmon
    • 1
  • N Connors
    • 1
  1. 1.Biocatalysis and Fermentation Development, Merck Research Laboratories, Rahway, NJ, USAUS
  2. 2.Process Research, Merck Research Laboratories, Rahway, NJ, USAUS

Personalised recommendations