Epigenetic manipulation for secondary metabolite activation in endophytic fungi: current progress and future directions

Figures & data

Figure 1. The schematic representation showcases various approaches utilised in the study of chromatin modification. Techniques such as HPLC (High-Performance Liquid Chromatography), GC-MS (Gas Chromatography-Mass Spectrometry), and NMR (Nuclear Magnetic Resonance) spectroscopy are employed to gather information regarding alterations in metabolite profiling. These techniques contribute valuable insights into the characterisation and analysis of chromatin modifications.

Figure 2. Chemical structure of epigenetic modifiers, such as 5-azacytidine (1), 5-aza-2’-deoxycytidine (2), suberohydroxamic acid (SBHA) (3), Sodium butyrate (4), Suberoylanilide hydroxamic acid (SAHA) (5), Trichostatin A (6), and Valproic acid (7) that are being used for the enhancement of secondary metabolite production. The chemical structure of metabolites obtained through epigenetic modifications, such as Cytosporone E (8), Dendrodolide E (9), Dendrodolide G (10), Dendrodolide I (11), Fumiquinazoline C (12), Vermistatin (13), Alternariol (14), Resveratrol (15), Eupenicinicol C (16), (Z)-9-octadecenoic acid (17), Dihydrovermistatin (18), 12-methyl-tetradecanoic acid (19), Cytosporone B (20), Isosulochrin (21), and Eupenicinicol D (22).

Table 1. List of epigenetic modifiers, their mode of action and elicited compounds.

S. No.	Endophytic fungi	Host plant	Epigenetic modifier	Mechanism of action	Elicit compounds	Reference
1.	Leucostoma persoonii	Rhizophora mangle	5-azacytidine (1)	Inhibition of DNA methyl transferase	Cytosporone B (20)	Beau et al. (2012)
2.	Leucostoma persoonii	Rhizophora mangle	Sodium butyrate (4)	Inhibition of HDAC of classes I and II	Cytosporone E (8)	Beau et al. (2012)
3.	Dimorphosporicola tragani	Arthrocnemum macrostachyum	5-azacytidine (1), Valproic acid (7)	Inhibition of DNA methyl transferase, Inhibition of HDAC of classes I and II	Dendrodolide E (9), G (10), I (11)	González-Menéndez et al. (2019)
4.	Pestalotiopsis crassiuscula	Fragaria chiloensis	5-azacytidine (1)	Inhibition of DNA methyl transferase	4,6-dihydroxy-3,7-dimethylcoumarin, pestalotiopyrone G and 2′-hydroxy-6′-hydroxymethyl-4′-methylphenyl 2,6-dihydroxy-3-(2-isopentenyl)benzoate	Yang et al. (2014)
5.	Aspergillus fumigatus	Grewia asiatica	Valproic acid (7)	Inhibition of HDAC of classes I and II	Fumiquinazoline C (12)	Magotra et al. (2017)
6.	Chaetomium sp.	Sapium ellipticum	SAHA (5) or 5-azacytidine (1)	Inhibition of HDAC of classes I and II, Inhibition of DNA methyl transferase	Isosulochrin (21)	Akone et al. (2016)
7.	Eupenicillium sp.	Xanthium sibiricum	NAD+-dependent histone deacetylase inhibitor	Inhibition of HDAC of class I	Eupenicinicol C (16) and D (22)	Li et al. (2017)
8.	Alternaria sp.	Datura stramonium	SAHA (5)	Inhibition of HDAC of classes I and II	Alternariol (14), alternariol-5-O-methyl ether, 3′-hydroxy-5-methoxyalternariol, altenusin, (5S, 8S)-tenuazonic acid	Sun et al. (2012)
9.	Phoma sp.	Parkinsonia microphylla		Inhibition of HDAC of classes I and II	Vermistatin (13) and dihydrovermistatin (18)	Gubiani et al. (2017)
10.	Penicillium herquei	Cordyceps sinensis	5-aza-2-deoxycytidine (2)	Inhibition of DNA methyltransferase	(S)-6-(sec-butyl)-5-(hydroxymethyl)-4-methoxy-2 H-pyran-2-one and (5S,7 R)-7-ethyl-4,5-dimethoxy-7-methyl-5,7-dihydro-2 H-furo[3,4-b]pyran-2-one	Guo et al. (2020)
11.	A. niger	Terminalia catappa	5-azacytidine (1)	Inhibition of DNA methyl transferase	(Z)-9-octadecenoic acid (17) and 12-methyl-tetradecanoic acid (19)	Toghueo et al. (2016)

Figure 3. The diagram illustrates different strategies employed to enhance the production of fungal endophyte-associated metabolites. One approach involves the use of chemical elicitors to boost the production of secondary metabolites. Another approach utilises the CRISPR-Cas9 mediated genome editing technique, which enables targeted modifications to the fungal strain’s genome, ultimately leading to enhanced metabolite production.

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