Dataset Information

Draft Genome Sequence of the Fungus Penicillium brasilianum (Strain LaBioMMi 136), a Plant Endophyte from Melia azedarach.

ABSTRACT: Penicillium brasilianum (strain LaBioMMi 136) has been reported to be a great producer of secondary metabolites and a source of enzymes of biotechnological interest. Here, we report the draft genome sequence of P. brasilianum (strain LaBioMMi 136), isolated as an endophyte from the plant Melia azedarach (family Meliaceae).

SUBMITTER: Fill TP

PROVIDER: S-EPMC6284728 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Draft Genome Sequence of the Fungus <i>Penicillium brasilianum</i> (Strain LaBioMMi 136), a Plant Endophyte from <i>Melia azedarach</i>.

Fill Taícia Pacheco TP Baretta Jéssica Fernanda JF de Almeida Luiz Gonzaga Paula LGP Malavazi Iran I Cerdeira Louise Teixeira LT Samborskyy Markiyan M de Vasconcelos Ana Tereza Ribeiro ATR Leadlay Peter P Rodrigues-Filho Edson E

Microbiology resource announcements 20181129 21

Penicillium brasilianum (strain LaBioMMi 136) has been reported to be a great producer of secondary metabolites and a source of enzymes of biotechnological interest. Here, we report the draft genome sequence of P. brasilianum (strain LaBioMMi 136), isolated as an endophyte from the plant Melia azedarach (family Meliaceae). ...[more]

PMID: 30533840

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Project description:BACKGROUND:MAPK/ERK kinases transmit signals from many growth factors/kinase receptors during normal cell growth/differentiation, and their dysregulation is a hallmark of diverse types of cancers. A plethora of drugs were developed to block this kinase pathway for clinical application. With the exception of a recently identified agent, EQW, most of these inhibitors target upstream factors but not ERK1/2; no activator of ERK1/2 is currently available. METHOD:A library of compounds isolated from medicinal plants of China was screened for anti-cancer activities. Three limonoid compounds, termed A1541-43, originally isolated from the plant Melia azedarach, exhibiting strong anti-leukemic activity. The anti-neoplastic activity and the biological target of these compounds were explored using various methods, including western blotting, flow cytometry, molecular docking and animal model for leukemia. RESULTS:Compounds A1541-43, exhibiting potent anti-leukemic activity, was shown to induce ERK1/2 phosphorylation. In contrast, the natural product Cedrelone, which shares structural similarities with A1541-43, functions as a potent inhibitor of ERK1/2. We provided evidence that A1541-43 and Cedrelone specifically target ERK1/2, but not the upstream MAPK/ERK pathway. Computational docking analysis predicts that compounds A1541-43 bind a region in ERK1/2 that is distinct from that to which Cedrelone and EQW bind. Interestingly, both A1541-43, which act as ERK1/2 agonists, and Cedrelone, which inhibit these kinases, exerted strong anti-proliferative activity against multiple leukemic cell lines, and induced robust apoptosis as well as erythroid and megakaryocytic differentiation in erythroleukemic cell lines. These compounds also suppressed tumor progression in a mouse model of erythroleukemia. CONCLUSIONS:This study identifies for the first time activators of ERK1/2 with therapeutic potential for the treatment of cancers driven by dysregulation of the MAPK/ERK pathway and possibly for other disorders.

Dataset Information

Draft Genome Sequence of the Fungus Penicillium brasilianum (Strain LaBioMMi 136), a Plant Endophyte from Melia azedarach.

Publications

Draft Genome Sequence of the Fungus <i>Penicillium brasilianum</i> (Strain LaBioMMi 136), a Plant Endophyte from <i>Melia azedarach</i>.

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