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United States Department of Agriculture

Agricultural Research Service

Research Project: CONTROL OF TOXIC ENDOPHYTIC FUNGI WITH BACTERIAL ENDOPHYTES AND REGULATION OF BACTERIAL METABOLITES FOR NOVEL USES IN FOOD SAFETY

Location: Toxicology and Mycotoxin Research

Title: Metabolites from the endophytic fungus Sporormiella minimoides isolated from Hintonia latiflora

Authors
item Leyte-Lugo, Martha -
item Figueroa, Mario -
item Gonzalez, Maria Delcarmen -
item Glenn, Anthony
item Gonzalez-Andrade, Martin -
item Mata, Rachel -

Submitted to: Phytochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 7, 2013
Publication Date: September 28, 2013
Citation: Leyte-Lugo, M., Figueroa, M., Gonzalez, M., Glenn, A.E., Gonzalez-Andrade, M., Mata, R. 2013. Metabolites from the endophytic fungus Sporormiella minimoides isolated from Hintonia latiflora. Phytochemistry. 96:273-278. DOI: 10.1016/j.phytochem.2013.09.006.

Interpretive Summary: The plant Hintonia latiflora is noted in Mexico for its anti-diabetic medicinal properties. As part of a study isolating fungi that live within this plant (i.e., endophytes), Sporormiella minimoides was isolated and evaluated for its production of metabolites in culture. Three new polyketide-type compounds were extracted and identified, along with three previously known polyketides. The six compounds were assessed for their ability to inhibit calmodulin. This was done using a novel fluorescent biosensor developed to measure the interaction of the metabolites with calmodulin. Cells use this enzyme to break apart complex carbohydrates to generate glucose, which is then absorbed by the cells. Inhibition of calmodulin is an important strategy for the treatment of diabetes, since slower absorption of glucose prevents spikes in blood sugar. Therefore, much interest exists in identifying new, effective inhibitory compounds as possible drugs for the treatment of diabetes. Only one of the polyketides, 5-hydroxy-2,7-dimethoxy-8-methylnaphthoquinone, showed significant interaction with calmodulin. This is the first report of a naphthoquinone-type compound as a calmodulin inhibitor.

Technical Abstract: An extract of the solid cultures of Sporormiella minimoides (Sporormiaceae) isolated as an endophytic fungus from Hintonia latiflora (Rubiaceae), yielded three polyketides, 3,6-dimethoxy-8-methyl-1H,6H-benzo[de]isochromene-1,9-dione, 3-hydroxy-1,6,10-trimethoxy-8-methyl-1H,3H-benzo[de]isochromen-9-one, and 5-hydroxy-2,7-dimethoxy-8-methylnaphthoquinone, along with three known compounds, corymbiferone, ziganein, and brocaenol B. Their structures were characterized by spectrometric and spectroscopic methods. So as to be consistent the literature reports, 3,6-dimethoxy-8-methyl-1H,6Hbenzo[de]isochromene-1,9-dione and 3-hydroxy-1,6,10-trimethoxy-8-methyl-1H,3Hbenzo[de]isochromen-9-one were given the trivial names of corymbiferone C and corymbiferan lactone E, respectively. All isolates were tested as potential human calmodulin (hCaM) inhibitors using the novel fluorescent biosensor hCaM V91C-mBBr, but only 5-hydroxy-2,7-dimethoxy-8-methylnaphthoquinone quenched significantly the extrinsic fluorescence of this biosensor, with a dissociation constant (Kd) value of 1.55 µM. Refined docking analysis predicted that 5-hydroxy-2,7-dimethoxy-8-methylnaphthoquinone could also be bound to hCaM at site I displaying hydrophobic interactions with Phe19 and 68, Met51, 71, and 72, and Ile52 and 63 residues.

Last Modified: 8/30/2014
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