title: Production of mutagenic metabolites by Metarhizium anisopliae.
abstract: NG-391 (1) and NG-393 (2), previously reported from undescribed Fusarium species as nerve-cell growth stimulants, were identified from fermentation extracts of the entomopathogenic fungus Metarhizium anisopliae. These compounds are 7-desmethyl analogues of fusarin C and (8Z)-fusarin C, mutagenic toxins from Fusarium species that contaminate corn. A mutant strain of M. anisopliae (KOB1-3) overproduces 1 and 2 by ca. 10-fold relative to the wild-type strain, ARSEF 2575, from which it was derived. Overproduction of these compounds in KOB1-3 imparts a yellow pigmentation to the culture medium of the fungus. These compounds were inactive at 100 mug/disk in antimicrobial disk diffusion assays. Compound 1 was inactive at 100 ppm in a mosquitocidal assay. However, like their fusarin analogues, 1 and 2 exhibited potent S9-dependent mutagenic activity in the Salmonella mutagenicity test. Discovery of these highly mutagenic mycotoxins in M. anisopliae suggests that screening for production of NG-391 and NG-393 in strains that are used as biocontrol agents would be a prudent course of action. The impact of these findings on the use of M. anisopliae as a biocontrol agent is currently unknown and requires further investigation.
authors.affiliation: USDA-ARS-Plant Protection Research Unit, Tower Road, Ithaca, New York 14853, USA. sbk1@cornell.edu
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Krasnoff
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Sommers
authors.forename: Yong-Sun
authors.initials: YS
authors.lastname: Moon
authors.forename: Bruno G G
authors.initials: BG
authors.lastname: Donzelli
authors.forename: John D
authors.initials: JD
authors.lastname: Vandenberg
authors.forename: Alice C L
authors.initials: AC
authors.lastname: Churchill
authors.forename: Donna M
authors.initials: DM
authors.lastname: Gibson
mesh_terms: D001203:Ascomycota / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005285:Fermentation; D005670:Fusarium / Q000378:metabolism*; D007769:Lactams / Q000737:chemistry / Q000378:metabolism; D007783:Lactones / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D009183:Mycotoxins / Q000096:biosynthesis*; D011090:Polyenes / Q000737:chemistry / Q000378:metabolism
chemical_list: D007769:Lactams; D007783:Lactones; D009153:Mutagens; D009183:Mycotoxins; D011090:Polyenes; C080196:fusarin Z; C041403:fusarin C