Differential metabolism of diastereoisomeric diterpenes by Preussia minima, found as endophytic fungus in Cupressus lusitanica

• Published in: Bioorganic chemistry 2018-08, Vol.78, p.436-443
• Main Authors: ud Din, Zia, de Medeiros, L.S., Abreu, L.M., Pfenning, Ludwig H., Lopes Jymeni, D.B., Rodrigues-Filho, E.
• Format: Article
• Language: English
• Subjects: Biotransformation; Cupressus lusitanica; Cytochrome P450; Diterpene; Endophytic; Preussia minima
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2018.04.003

[Display omitted] •The fungus Preussia minima was found as endophytic in the tree Cupressus lusitanica.•Diterpenes sandaracopimaric and ent-isopimaric acids were biotransformaed by P. minima.•The biotransformation resulted in two set of differently oxidized diterpenes.•The pattern of oxidation was rationalized based on action of Cytochrome P450 enzymes.•P. minima converted ent-isopimaric acid in one isomer of sphaeropsidin C phytotoxin. The plant diastereoisomeric diterpenes ent-pimara-8(14)-15-dien-19-oic acid, obtained from Viguiera arenaria, and isopimara-8(14)-15-dien-18-oic acid, isolated from Cupressus lusitanica, were distinctly functionalized by the enzymes produced in whole cell cultures of the fungus Preussia minima, isolated from surface sterilized stems of C. lusitanica. The ent-pimaradienoic acid was transformed into the known 7β-hydroxy-ent-pimara-8(14)-15-dien-19-oic acid, and into the novel diterpenes 7-oxo-8 β-hydroxy-ent-pimara-8(14)-15-dien-19-oic and 7-oxo-9β-hydroxy-ent-pimara-8(14)-15-dien-19-oic acids. Isopimara-8(14)-15-dien-18-oic acid was converted into novel diterpenes 11α-hydroxyisopimara-8(14)-15-dien-18-oic acid, 7β,11α-dihydroxyisopimara-8(14)-15-dien-18-oic acid, and 1β,11α-dihydroxyisopimara-8(14)-15-dien-18-oic acid, along with the known 7β-hydroxyisopimara-8(14)-15-dien-18-oic acid. All compounds were isolated and fully characterized by 1D and 2D NMR, especially 13C NMR. The diterpene bioproduct 7-oxo-9β-hydroxy-ent-pimara-8(14)-15-dien-19-oic acid is an isomer of sphaeropsidin C, a phytotoxin that affects cypress trees produced by Shaeropsis sapinea, one of the main phytopathogen of Cupressus. The differential metabolism of the diterpene isomers used as substrates for biotransformation was interpreted with the help of computational molecular docking calculations, considering as target enzymes those of cytochrome P450 group.