Affiliation:
1. 0000 0001 0671 255X grid.266860.c Department of Chemistry and Biochemistry University of North Carolina at Greensboro P.O. Box 26170 27402 Greensboro NC USA
2. grid.427032.0 Mycosynthetix, Inc. 505 Meadowlands Drive, Suite 103 27278 Hillsborough NC USA
Abstract
Abstract
Verticillins are a group of epipolythiodioxopiperazine alkaloids that have displayed potent cytotoxicity. To evaluate their potential further, a larger supply of these compounds was needed for both in vivo studies and analogue development via semisynthesis. To optimize the biosynthesis of these secondary metabolites, their production was analyzed in two different fungal strains (MSX59553 and MSX79542) under a suite of fermentation conditions. These studies were facilitated by the use of the droplet-liquid microjunction-surface sampling probe (droplet probe), which enables chemical analysis in situ directly from the surface of the cultures. These experiments showed that the production of verticillins was greatly affected by growth conditions; a significantly higher quantity of these alkaloids was noted when the fungal strains were grown on an oatmeal-based medium. Using these technologies to select the best among the tested growth conditions, the production of the verticillin analogues was increased while concomitantly decreasing the time required for fermentations from 5 weeks to about 11 days. Importantly, where we could previously supply 5–10 mg every 6 weeks, we are now able to supply 50–150 mg quantities of key analogues per month via laboratory scale fermentation.
Graphical abstract
Funder
National Cancer Institute
Publisher
Oxford University Press (OUP)
Subject
Applied Microbiology and Biotechnology,Biotechnology,Bioengineering
Cited by
19 articles.
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