Harzianone Biosynthesis by the Biocontrol Fungus Trichoderma

Analysis of the volatile terpenes produced by seven fungal strains of the genus Trichoderma by use of a closed-loop stripping apparatus (CLSA) revealed a common production of harzianone, a bioactive, structurally unique diterpenoid consisting of a fused tetracyclic 4,7,5,6-membered ring system. The terpene cyclization mechanism was studied by feeding experiments using selectively C-13- and H-2-labeled synthetic mevalonolactone isotopologues, followed by analysis of the incorporation patterns by (CNMR)-C-13 spectroscopy and GC/MS. The structure of harzianone was further supported from a C-13,(CCOSY)-C-13 experiment of the in-vivo-generated fully C-13-labeled diterpene.