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 marine-derived fungi.
Highlights
Marine fungi have been proved to possess the potential ability to produce structurally unique and biologically active secondary metabolites (Blunt et al, 2018)
The results showed that a histone deacetylase (HDAC) inhibitor, sodium butyrate, induced significant changes of the fungal metabolic profile
Chemical investigation of the EtOAc extract led to the isolation of three new terpenoids, including one novel chlorinated cleistanthane diterpenoid, harzianolic acid A (1), one harziane diterpenoid, harzianone E (2), and one cyclonerane sesquiterpenoid, 3,7,11-trihydroxy-cycloneran (3), together with 11 known sesquiterpenoids, including eight cyclonerane sesquiterpenoids, methyl 3,7-dihydroxy-15cycloneranate (4) (Song et al, 2018), catenioblin C (5) (Wu et al, 2012), ascotrichic acid (6) (Xie et al, 2013), cyclonerotriol (7) (Kasitu et al, 1992), (10E)-12-acetoxy-10-cycloneren-3,7-diol (8) (Fang et al, 2018), cyclonerodiol (9) (Nozoe et al, 1970), cyclonerodiol oxide (10) (Fujita et al, 1984) and epicyclonerodiol oxide (11) (Fujita et al, 1984), one african sesquiterpenoid, ophioceric acid (12) (Reátegui et al, 2005), and two acoranetype sesqiuterpenoids, ent-trichoacorenol (13) (Brock and Dickschat, 2011) and trichoacorenol (14) (Huang et al, 1995) (Figure 2)
Summary
Marine fungi have been proved to possess the potential ability to produce structurally unique and biologically active secondary metabolites (Blunt et al, 2018). In order to solve this challenge, a number of manipulations have been used to regulate the production of secondary metabolites from fungi, such as One strain many compounds (OSMAC) (Pan et al, 2019), co-culture (Yu et al, 2019), interspecies crosstalk (Wang et al, 2019), and heterologous expression (Huo et al, 2019; Zhang et al, 2019) Among these methods, chemical epigenetic manipulation has been demonstrated to be a promising strategy to wake the silent biosynthetic gene clusters to obtain novel compounds and has been applied to the marine fungi (Asai et al, 2013). Fungus with a combination of HDAC inhibitor (SAHA) and DNA methyltransferase (DNMT) inhibitor (5-azacytidine) resulted in the discovery of three new eremophilane-type sesquiterpenoids with nitric oxide inhibitory activities (Niu et al, 2018) These cases might demonstrate that chemical epigenetic manipulation could efficiently excavate novel secondary metabolites from marine-derived fungi. The successful examples of chemical epigenetic manipulation applied to marine-derived fungi are not abundant enough to confirm the conclusion
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
