Chemogenomics driven discovery of endogenous polyketide anti-infective compounds from endosymbiotic Emericella variecolor CLB38 and their RNA secondary structure analysis

Abstract

In the postgenomic era, a new strategy for chemical dereplication of polyketide anti-infective drugs requires novel genomics and chromatographic strategies. An endosymbiotic fungal strain CLB38 was isolated from the root tissue of Combretum latifolium Blume (Combretaceae) which was collected from the Western Ghats of India. The isolate CLB38 was then identified as Emericella variecolor by its characteristic stellate ascospores culture morphology and molecular analysis of ITS nuclear rDNA and intervening 5.8S rRNA gene sequence. ITS2 RNA secondary structure modeling clearly distinguished fungal endosymbiont E. variecolor CLB38 with other lifestyles in the same monophyletic clade. Ethyl acetate fraction of CLB38 explored a broad spectrum of antimicrobial activity against multidrug resistant pathogens. Biosynthetic PKS type-I gene and chromatographic approach afford two polyketide antimicrobial compounds which identified as evariquinone and isoindolones derivative emerimidine A. MIC of purified compounds against test microorganisms ranged between 3.12 μg/ml and 12.5 μg/ml. This research highlights the utility of E. variecolor CLB38 as an anticipate source for anti-infective polyketide metabolites evariquinone and emerimidine A to combat multidrug resistant microorganisms. Here we demonstrates a chemogenomics strategy via the feasibility of PKS type-I gene and chromatographic approach as a proficient method for the rapid prediction and discovery of new polyketides compounds from fungal endosymbionts.

Integration of Fungus-Specific CandA-C1 into a Trimeric CandA Complex Allowed Splitting of the Gene for the Conserved Receptor Exchange Factor of CullinA E3 Ubiquitin Ligases in Aspergilli

“…S3H), which is in accordance with the literature (51). The similarity between the UV-Vis spectra of cichorine and emerimidine, which fit very well with the literature, indicates that the two have the same core structure (51, 52). Cichorine is synthesized from a nonreducing polyketide synthase, CicF (AN6448) (52).…”

“…The thin-layer chromatogram of the extracts from asexually and sexually developed Δ candA-C and Δ candA-N mutants showed a blue spot at 366 nm at an R f of 0.43 (Fig. S3H), which is in accordance with the literature (51). The similarity between the UV-Vis spectra of cichorine and emerimidine, which fit very well with the literature, indicates that the two have the same core structure (51, 52).…”

“…Emerimidine produced by Emericella variecolor CLB38 was shown to have antimicrobial activity against multidrug-resistant microorganisms like Bacillus subtilis and Staphylococcus aureus but also antifungal activity against Candida albicans and A. fumigatus (51). The thin-layer chromatogram of the extracts from asexually and sexually developed Δ candA-C and Δ candA-N mutants showed a blue spot at 366 nm at an R f of 0.43 (Fig.…”

Induction of Cryptic and Bioactive Metabolites through Natural Dietary Components in an Endophytic Fungus Colletotrichum gloeosporioides (Penz.) Sacc.

“…Endophytic fungi are also well known producer of other potential natural compounds of agricultural, industrial and pharmaceutical interest. Some recent reviews have thoroughly discussed the considerable numbers of antibacterial compounds isolated from endophytic microbes and their efficacy and probable usages (Mishra et al, 2012, 2016; Deshmukh et al, 2015; Rao et al, 2017). More than 100 anticancer compounds have been reported alone from fungal endophytes between the period of 1990–2010 (Kharwar et al, 2011).…”