DMSO suppresses duclauxin biosynthetic pathway in Talaromyces sp. (strain IQ-313) and untaps terpenoids, polyketides and meroterpenoids biosynthesis

Abstract

Talaromyces sp. (strain IQ-313) produces duclauxin-type molecules under standard fermentation conditions in rice and oat cereal. Such molecules are of great interest due to their structural complexity and biological activity. Interestingly, application of an OSMAC (One Strain Many Compounds) approach, revealed that the biosynthetic machinery of this fungus can be directed towards the production of other types of molecules, while completely suppressing the biosynthesis of duclauxin (1). To exploit the metabolic potential of Talaromyces sp. (strain IQ-313), it was grown on solid media supplemented with dimethyl sulfoxide (DMSO), an ectopic epigenetic modulator. Metabolomic analysis of the fermentation extract from the strain grown under standard and DMSO-supplemented conditions, using molecular networking, revealed notable differences in the profiles. Chemical investigation of the extract obtained under abiotic stress led to the isolation and characterization of 15 molecules not detected under standard conditions, including nine polyketides, one sesquiterpenoid, two sesterterpenoids, and three meroterpenoids. Among these, talaromophilane (2), an eremophilane sesquiterpenoid, and talaroisochromane (8), an oxoisochromen, have not been previously reported in the literature. The structures of all isolates were established using a combination of spectroscopic and spectrometric data. The absolute configuration of compound 2 was established based on the analysis of NOESY interactions and by comparison of the experimental and theoretical electronic circular dichroism (ECD) curves.