Terpenoids From the Coral-Derived Fungus Trichoderma harzianum (XS-20090075) Induced by Chemical Epigenetic Manipulation

Abstract

The soft coral-derived fungus Trichoderma harzianum (XS-20090075) was found to be a potential strain to produce substantial new compounds in our previous study. In order to explore its potential to produce more metabolites, chemical epigenetic manipulation was used on this fungus to wake its sleeping genes, leading to the significant changes of its secondary metabolites by using a histone deacetylase (HDAC) inhibitor. The most obvious difference was the original main products harziane diterpenoids were changed into cyclonerane sesquiterpenoids. Three new terpenoids were isolated from the fungal culture treated with 10 µM sodium butyrate, including cleistanthane diterpenoid, harzianolic acid A (1), harziane diterpenoid, harzianone E (2), and cyclonerane sesquiterpenoid, 3,7,11-trihydroxy-cycloneran (3), together with 11 known sesquiterpenoids (4-14). The absolute configurations of 1-3 were determined by single-crystal X-ray diffraction, ECD and OR calculations, and biogenetic considerations. This was the first time to obtain cleistanthane diterpenoid and africane sesquiterpenoid from genus Trichoderma, and this was the first chlorinated cleistanthane diterpenoid. These results demonstrated that the chemical epigenetic manipulation should be an efficient technique for the discovery of new secondary metabolites from marinederived fungi.

Trichoderma: A Treasure House of Structurally Diverse Secondary Metabolites With Medicinal Importance

“…Induced by a chemical epigenetic manipulation strategy, a new cyclonerane, 3,7,11-trihydroxy-cycloneran (44), was produced by the marine fungus T. harzianum (XS-20090075), which was isolated from soft corals (Shi T. et al, 2020). Cycloneranes having a monocyclic skeleton are reported to be produced from various fungal genera, such as Trichoderma, Aspergillus, Fusarium, Paecilomyces, and Trichothesium.…”

“…Deoxytrichodermaerin (90), an undescribed harziane lactone, was isolated from an endophyte T. longibrachiatum A-WH-20-2 of marine algae Laurencia okamurai (Zou et al, 2021). A new harziane diterpenoid, harzianone E (91), was obtained from the soft coral-sourced T. harzianum (XS-20090075) by chemical epigenetic manipulation strategy (Shi T. et al, 2020). A new harziane diterpene, 3R-hydroxy-9R,10R-dihydroharzianone (92), was produced by T. harzianum X-5 (Song et al, 2018).…”

“…104 and harzianes were structurally related diterpenes. Harzianolic acid A (105), characterized as a novel chlorinated cleistanthane diterpenoid, was isolated from the marine fungal strain T. harzianum (XS-20090075) (Shi T. et al, 2020). Tricyclic diterpenoids categorized to cleistanthanes were reported from Trichoderma for the first time.…”

“…Chemical epigenetic manipulation has also proven to be an effective method to activate cryptic BGCs. Therefore, it was applied to the marine fungal strain T. harzianum XS-20090075 to mine its potential to synthesize secondary metabolites (Shi T. et al, 2020). A histone deacetylase inhibitor, sodium butyrate at 10 µM, significantly changed its metabolic profile and gave rise to three undescribed terpenoids, including a cleistanthane 105, a harziane diterpenoid 91, and a cyclonerane sesquiterpenoid 44.…”

Benzyl Furanones and Pyrones from the Marine-Derived Fungus Aspergillus terreus Induced by Chemical Epigenetic Modification

“…In recent years, during our efforts to explore new bioactive marine natural products [ 9 ], chemical epigenetic manipulation has been applied to marine-derived fungi to mine their potential ability to produce metabolic products [ 9 , 10 , 11 , 12 , 13 , 14 ]. In our previous work, a series of thiodiketopiperazines and 3,4-dihydroisocoumarin derivatives were isolated from the starch liquid culture of A. terreus RA2905 derived from sea hare Aplysia pulmonica [ 15 ].…”