title: 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.
authors.affiliation: Microbial Drugs Laboratory, Department of Studies in Microbiology, University of Mysore, Manasagangotri, Mysore, Karnataka, India.
authors.forename: H C
authors.initials: HC
authors.lastname: Yashavantha Rao
authors.affiliation: Microbial Drugs Laboratory, Department of Studies in Microbiology, University of Mysore, Manasagangotri, Mysore, Karnataka, India.
authors.forename: Devaraju
authors.initials: D
authors.lastname: Rakshith
authors.affiliation: Department of Zoology, Bangalore University, Jnana Bharathi Campus, Bangalore, Karnataka, India.
authors.forename: Ballagere Puttaraju
authors.initials: BP
authors.lastname: Harini
authors.affiliation: Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore, Karnataka, India.
authors.forename: Doddahosuru Mahadevappa
authors.initials: DM
authors.lastname: Gurudatt
authors.affiliation: Microbial Drugs Laboratory, Department of Studies in Microbiology, University of Mysore, Manasagangotri, Mysore, Karnataka, India.
authors.forename: Sreedharamurthy
authors.initials: S
authors.lastname: Satish
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D029764:Combretaceae / Q000382:microbiology*; D004275:DNA, Ribosomal / Q000235:genetics; D032842:Emericella / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D054833:Isoindoles / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D061065:Polyketides / Q000737:chemistry / Q000494:pharmacology; D012331:RNA, Fungal / Q000235:genetics; D013559:Symbiosis
chemical_list: D000890:Anti-Infective Agents; D004275:DNA, Ribosomal; D054833:Isoindoles; D061065:Polyketides; D012331:RNA, Fungal; C561991:emerimidine