Isolation, (bio)synthetic studies and evaluation of antimicrobial properties of drimenol-type sesquiterpenes of Termitomyces fungi

Abstract

Macrotermitinae termites have farmed fungi in the genus Termitomyces as a food source for millions of years. However, the biochemical mechanisms orchestrating this mutualistic relationship are largely unknown. To deduce fungal signals and ecological patterns that relate to the stability of this symbiosis, we explored the volatile organic compound (VOC) repertoire of Termitomyces from Macrotermes natalensis colonies. Results show that mushrooms emit a VOC pattern that differs from mycelium grown in fungal gardens and laboratory cultures. The abundance of sesquiterpenoids from mushrooms allowed targeted isolation of five drimane sesquiterpenes from plate cultivations. The total synthesis of one of these, drimenol, and related drimanes assisted in structural and comparative analysis of volatile organic compounds (VOCs) and antimicrobial activity testing. Enzyme candidates putatively involved in terpene biosynthesis were heterologously expressed and while these were not involved in the biosynthesis of the complete drimane skeleton, they catalyzed the formation of two structurally related monocyclic sesquiterpenes named nectrianolins.

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

“…This enzyme shares a 50% sequence similarity with SsDMS, including a conserved “DXDD” motif, indicating its potential as a class II sesquiterpene synthase (Figure S8, Supporting Information File 1 ) [ 20 ]. Further analysis of adjacent genes revealed a Nudix hydrolase located upstream of the putative DMS, similar to the reported situation with SsDMS [ 19 ]. Inspection of the BGC identified additional three P450s.…”

Class II terpene cyclases: structures, mechanisms, and engineering

“…Class II TCs are involved in the early-stage biosynthetic routes of many natural products with examples seen and characterized in bacteria, fungi, and plants. 13,20,39,42,59,166,167 In many pathways, the substrates of these enzymes are isoprenoid diphosphates. As class II TCs leave the diphosphate moiety intact, the products are primed for further structural diversification by class I TCs.…”

Therapeutic Potential of Fungal Terpenes and Terpenoids: Application in Skin Diseases

“…Drimenol, a sesquiterpene isolated from the fungus Termitomyces sp., demonstrates anti-fungal activity against C. albicans and Penicillium notatum . Moreover, it exhibits antibacterial efficacy against S. aureus and Pseudomonas aeruginosa [ 64 ]. Sesquiterpenoids from the Sanghuangporus sp.…”