ARS | Publication request: Metacridamides A and B from the biocontrol fungus metarhizium acridum

Submitted to: American Society of Pharmacognosy
Publication Type: Abstract Only
Publication Acceptance Date: July 29, 2011
Publication Date: July 29, 2011
Citation: Krasnoff, S., Englich, U., Miller, P., Shuler, M.L., Glahn, R.P., Donzelli, B.G., Gibson, D.M. 2011. Metacridamides A and B from the biocontrol fungus metarhizium acridum. American Society of Pharmacognosy. p. 325.

Technical Abstract: Metarhizium acridum, an entomopathogenic fungus, has been commercialized and used successfully for biocontrol of grasshopper pests in Africa and Australia. As part of an effort to catalog the secondary metabolites of this fungus we discovered that its conidia produce two novel 17-membered macrocycles, metacridamides A (1) and B (2), which consist of a Phe unit condensed with a nonaketide, the likely product of a polyketide synthase. Planar structures were elucidated by a combination of mass spectrometric and NMR techniques. Following hydrolysis of 1, chiral amino acid analysis established the Phe unit as L-configured. A crystal structure provided the absolute configuration of the eight remaining stereogenic centers in 1. Metacridamide A, but not B, exhibited moderate cytotoxicity (EC50s < 10µM) against Caco-2 (epithelial colorectal adenocarcinoma), MCF-7 (breast cancer), and HepG2/C3A (hepatoma) cell lines. Neither analog showed antimicrobial or insecticidal activity. The function of the compounds for the producing organism remains unknown.