The supplementation of a DNA methyltransferase inhibitor, 5-azacytidine (5-AZ), to the culture medium of Penicillium funiculosum, dramatically altered its metabolic profiles. Analysis of the culture broth extract led to the isolation of two new prenyleudesmane diterpenoids (1-2). The isolated compounds were further evaluated for their cytotoxic and antibacterial activities. Our findings confirmed that the use of chemical epigenetic modifiers is an effective technique for promoting the expression of silent biosynthetic pathways to produce unique secondary metabolites.
CichewiczRH. (2010) Epigenome manipulation as a pathway to new natural product scaffolds and their congeners. Natural Product Reports, 27, 11–22
3.
WilliamsRB, HenriksonJC, HooverAR, LeeAE, CichewiczRH. (2008) Epigenetic remodeling of the fungal secondary metabolome. Organic & Biomolecular Chemistry, 7, 1895–1897
4.
HenriksonJC, HooverAR, JoynerPM, CichewiczRH. (2009) A chemical epigenetics approach for engineering the in situ biosynthesis of a cryptic natural product from Aspergillus niger. Organic & Biomolecular Chemistry, 7, 435–438
5.
WangX, FilhoJGS, HooverAR, KingJB, EllisTK, PowellDR, CichewiczRH. (2010) Chemical epigenetics alters the secondary metabolite composition of guttate excreted by an Atlantic-forest-soil-derived Penicillium citreonigrum. Journal of Natural Products, 73, 942 – 948
6.
AsaiT, YamamotoT, OshimaY. (2011) Histone deacetylase inhibitor induced the production of three novel prenylated tryptophan analogs in the entomopathogenic fungus, Torrubiella luteorostrata. Tetrahedron Letters, 52, 7042–7045.
7.
ChengSY, ChuangCT, WangSK, WenZH, ChiouSF, HsuCH, DaiCF, DuhCY. (2010) Antiviral and anti-inflammatory diterpenoids from the soft coral Sinularia gyrosa. Journal of Natural Products, 73, 1184–1187
8.
MosmannT. (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assaysJournal of Immunological Methods, 65, 55–63.
9.
ReedLJ, MuenchHA. (1938) A simple method of estimating fifty percent endpoints. The American Journal of Hygiene, 27, 493–497.
