Phenalenones: insight into the biosynthesis of polyketides from the marine alga-derived fungus Coniothyrium cereale

Abstract

The marine alga-derived fungus Coniothyrium cereale is a prolific producer of phenalenones. These polyketides were shown to possess antimicrobial effects and inhibitory activity towards the protease human leucocyte elastase (HLE). The current study focused on the biosynthesis of eight different structural types of phenalenones, comprising the natural products rousselianone A' (1), coniosclerodin (3), cereolactam (12), cereoaldomine (15), and trypethelone (16). Solid agar cultures of C. cereale were used to follow up the incorporation of [1-(13)C] labeled acetate into these metabolites. Taking the respective mechanisms of polyketide metabolism into account, the labeling pattern was interpreted, thus providing a hypothesis for the biosynthetic formation of the phenalenones. The polyketide skeleton of the phenanthrene-based compound cereolactam is proposed to be formed through degradation of a heptaketide by loss of two carbon atoms.

Biosynthetic Studies on Acetosellin and Structure Elucidation of a New Acetosellin Derivative

“…The E. nigrum strain 749, however, does effectively produce the natural products of interest exclusively on solid media. During this project, we thus applied a methodology using solid agar-based media, recently developed in our laboratory, where [1-13 C]labeled sodium acetate solution is added periodically onto the top of the growing fungal culture [9].…”

Phenalenones from a Marine-Derived Fungus Penicillium sp.

“…Among these, phenalenones are a class of hexa- or heptaketides bearing a perinaphtenone-type tricyclic system [1]. As summarized in a recent comprehensive review, these compounds can have immense structural variations, such as homo- and heterodimerization, the incorporation of additional carbon frameworks, and a high degree of oxygenation and nitrogenation as well as being complexed with metals [2]. A frequently occurring variation is the incorporation of an isoprene unit by forming either a linear ether or a trimethylhydrofuran moiety, and this variation is well-represented in the herqueinones from Penicillium sp.…”

“…Fungi-derived phenalenone compounds have attracted significant interest due to their chemical structures, bioactivities, and biosynthesis [1]. With their diverse phylogenic origins, phenalenones are widely recognized as a representative group of fungal polyketides [1,2].…”

Application of Computational Chemical Shift Prediction Techniques to the Cereoanhydride Structure Problem—Carboxylate Complications

“…Fungi in particular are known to produce secondary metabolites with unique structures, often useful in drug discovery [1,2,3]. Unfortunately, the structures of many natural products have been misassigned initially, leading to frustration for chemists following up on these structures [4,5].…”