Abstract
With respect to fungal pathogenesis and virulence, fungal secondary metabolites are primary virulence factors in several fungus-plant interactions. This chapter explores the current state of knowledge on the production of secondary metabolites by the opportunistic human pathogen Aspergillus fumigatus. Several types of secondary metabolites have been isolated from A. fumigatus in vitro cultures, including fumitremorgins, verruculogen, fumigaclavines, fumagillin, helvolic acid, and gliotoxin, among other, less-studied compounds. Importantly, gliotoxin has been detected in the serum of patients with invasive pulmonary aspergillosis (IPA) and in experimental murine models of IPA. Overexpression of the nonribosomal peptide synthetase (NRPS) ftmA in A. fumigatus AF293.1 and A. nidulans resulted in accumulation of brevianamide F, the likely precursor of fumitremorgin biosynthesis. Like many other A. fumigatus-produced secondary metabolites, the potential role of helvolic acid in aspergillosis is unknown. Production of secondary metabolites is an energetically costly process involving many enzymatic steps. In fungi, signals generated in response to the environment are typically relayed through DNA-binding Cys2His2 zinc-finger proteins, including CreA for carbon signaling, AreA for nitrogen signaling, and PacC for pH signaling. Insight into signaling pathways linking growth, development, and secondary metabolism came from a key study in A. nidulans showing heterotrimeric G-protein activation simultaneously inhibits sporulation and production of the mycotoxin sterigmatocystin while promoting vegetative growth. Fungal secondary metabolites are important biomolecules with significant biological activities.
Published Version
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