TABLE 2.

Epigenetic induction of fungal biosynthetic gene clusters encoding secondary metabolites using small molecular compounds.

Fungal species	Culture conditions	Epigenetic modifier	Secondary metabolites produced	Activity profile	References
Cladosporium cladosporioides	Potato dextrose broth, 25°C, shaking at 100 rpm for 24 h, added elicitor and further incubation for 6 days	5-azacytidine, concentration range (0.1 μM-10 mM). used 10-fold less than MIC	three oxylipins [(9Z,12Z)-11-hydroxyoctadeca-9,12-dienoic acid, its methyl ester, and glycerol conjugate]	N/A	Williams et al., 2008
		SAHA, concentration range (0.1 μM-10 mM). used 10-fold less than MIC	perylenequinones, four known cladochromes (A, B, D and E) and two novel cladochromes (F and G), calphostin B	N/A
Diatrype disciformis		5-azacytidine, concentration range (0.1 μM-10 mM). used 10-fold less than MIC	two new polyketides (lunalides A and B)	N/A
Aspergillus niger ATCC 1015	Semi-solid vermiculite-based media#, 25°C, static condition (12 h light and 12 h dark) for 2 weeks	10 μM SAHA	nygerone A	N/A	Henrikson et al., 2009
Penicillium citreonigrum	Semi-solid vermiculite-based media#, 20°C, static conditions for 20 days	50 μM 5-azacytidine	six azaphilones (sclerotiorin, sclerotioramine, ochrephilone, dechloroisochromophilone 111, dechloroisochromophilone IV, 6-[(3E,5E)-5,7-dimethyl-2-methlenenona-3,5-dienyl]-2,4-dihydroxy-3-methylbenzaldehyde, pencolide) and two new meroterpenes (atlantinones A and B)	-moderate inhibition of Staphylococcus epidermidis (sclerotionin and sclerotioramine) -inhibition of Candida strains (sclerotioramine)	Wang et al., 2010
Leucostoma persoonia	Sabouraud dextrose agar, 30°C, static conditions for 3 weeks	100 μM sodium butyrate	enhanced production of cytosporones (B, C, and E) and unknown cytosporone R	cytosporone E active against Plasmodium falciparum and MRSA with low cytotoxicity in mammalian cells	Beau et al., 2012
		50 μM 5-azacytidine	• novel compound cytosporone R • enhanced production of known cytosporones B (360%), C (580%), and E (890%)
Alternaria sp.	Potato dextrose broth, 30°C, static conditions for 7 days	250 μM 5-azacytidine	mycotoxins including alternariol, alternariol-5-O-methyl ether, 3′-hydroxyalternariol-5-O-methyl ether, altenusin, tenuazonic acid, and altertoxin II.	N/A	Sun et al., 2012
		500 μM SBHA
Aspergillus clavatus	Fungal minimum media 1 (FM1): tryptic digested casein peptone or Fungal minimum media 2 (FM2): papaine-degested peptide	5 μM valproic acid	increased production of cytochalasin E (FM2 media), increased production of Pseurotin A (FM1 media) at 48 and 72 h	N/A	Zutz et al., 2013
		5 μM trichostin A	increased production of cytochalasin E (FM2 media), increase in Pseurotin A (FM1 media) at 48 h
		5 μM sodium butyrate
		5 μM 5-azacytidine	increased production of cytochalasin E (FM2 media), increase in Pseurotin A (FM1 media) at 72 h
Chaetomium indicum	Potato dextrose broth, 25°C, shaking at 150 rpm for 16 days	500 μM SAHA	enhanced the production of six novel prenylated aromatic polyketides, chaetophenols (A–F)	N/A	Asai et al., 2013
Chaetomium cancroideum	Potato dextrose broth, 25°C, shaking at 150 rpm for 14 days	50 μM nicotinamide	Three polyketides (chaetophenol G, cancrolides A and B)	N/A	Asai et al., 2016
Pestalotiopsis acacia	Potato dextrose broth, 30°C, shaking conditions for 7 days	500 μM SBHA and 500 μM 5-azacitidine	three novel aromatic compounds 1. 20-hydroxy-60-hydroxymethyl-40-methylphenyl-2,6-dihydroxy-3-(2-isopentenyl)benzoate; 2. 4,6-dihydroxy-7-hydroxymethyl-3-methylcoumarin 3. 4,6-dihydroxy-3,7-dimethylcoumarin five known polyketides (endocrocin, pestalotiollide B, pestalotiopyrone G, scirpyrone A and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone.	N/A	Yang et al., 2013
Endophytic Fusarium oxysporum strain R1	Potato dextrose broth, 28°C, static conditions for 7 days	500 μM SBHA	novel fusaric acid derivative: 5-Butyl-6-oxo-1,6-dihydropyridine-2-carboxylic acid and 5-(But-9-enyl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid	both fusaric acid derivatives showed no activity against Bacillus cereus while control (fusaric) shown activity	Chen et al., 2013
Penicillium funiculosum	Potato dextrose broth, 25°C, shaking conditions at for 2 weeks	100 μM 5-Azacytidine	induced the biosynthesis of two new prenyleudesmane diterpeniods	-no toxicity against three human cancer cell lines -not antimicrobial activity against Staphylococcus aureus, Bacillus thuringiensis, and B. subtilis	Liu et al., 2014
Chaetomium sp.	Milk Rice (Milch-Reis, ORYZA), 23°C, static conditions for 3–4 weeks. 2-days pre-incubation before adding elicitors	6 mM 5-azacytidine	induction of two new peaks compared to control, one identified as isosulochrin	N/A	Akone et al., 2016
		6 mM SAHA
Penicillium brevicompactum	Malt extract broth, 30°C, static conditions for 4 weeks	100 μM nicotinamide	p-anisic acid, p-anisic acid methyl ester, benzyl anisate, syringic acid, sinapic acid, acetosyringone, phenyl acetic acid, gentisaldehyde, and p-hydroxy benzaldehyde	N/A	El-Hawary et al., 2018
		0.01 M Sodium butyrate	enhanced the production of anthranilic acid and ergosterol peroxide	N/A
Cochliobolus lunatus (TA26-46)	Czapek Dox medium, Room temperature, 30 days	10 μM 5-Azacytidine	two new pyrones, (cochliobopyrones A and B), along with three isocoumarins and one chromone.	N/A	Wu et al., 2019
Penicillium brasilianum	Potato dextrose broth, 30°C, shaking at 70 rpm for 7 days	200 μM SAHA	Reduction of metabolites production such as brasiliamide A	N/A	Akiyama et al., 2020
		Nicotinamide
Aspergillus Calidoustus	Aspegillus complete medium (2.5% glucose, 0.5% yeast extract), 25°C, shaking at 150 rpm for 7 days	100 μM Vorinostat (or SAHA)	emericellamide A, emericellamide B, increased titer of phenylahistin	N/A	Aldholmi et al., 2020

SAHA, suberanilohydroxamic acid; SBHA, suberoylanilide hydroxamic acid; HDAC, histone deacetylase; DNMT, DNA methyltransferase; N/A, not available.