A dimeric pyrrocidine from Neonectria ramulariae is an inhibitor of prolyl oligopeptidase

Shiono, Yoshihito; Kosukegawa, Azusa; Koseki, Takuya; Murayama, Tetsuya; Kwon, Eunsang; Uesugi, Shota; Kimura, Ken

doi:10.1016/j.phytol.2011.10.008

Cited by 18 publications

(14 citation statements)

References 12 publications

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“…12). 61 It displayed specic non competitive inhibitory activity against prolyl oligopeptidase (serine protease), which is responsible for the inactivation of prolinecontaining neuropeptides, with a Ki of 2.6 mM. 1 0 ,2-Epoxypyrrocidine A (¼pyrrocidine C, 47), 62,63 2 0 -O-methylpyrrocidine B ( 48) and 2 0 -O-ethylpyrrocidine B (49) were isolated during the same work.…”

Section: Compounds Fungal Sources and Biological Activitiesmentioning

confidence: 97%

Hirsutellones and beyond: figuring out the biological and synthetic logics toward chemical complexity in fungal PKS-NRPS compounds

Ear

Nay

2013

Nat. Prod. Rep.

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Covering: up to early 2013. Fungal polyketides and their hybrid non ribosomal peptide derivatives are characterized by often striking structural features and biological activities. Their diversity and their complexity arise from highly organized and programmable biosynthetic pathways and have been challenged by many synthetic chemists. This review will conceptually illustrate how complexity can be generated, starting from a general biosynthetic purpose (the fundaments of PKS-NRPS assembly lines) and finally showing how the particular class of hirsutellone compounds has emerged from such processes in relation to post-elongation and secondary tailoring events. Synthetic efforts to produce these natural products will be described with a special emphasis on complexity-generating strategies and steps. Thus, the biosynthetic and synthetic works will be analyzed in a continuous flow, focusing on both the logic of Nature and organic chemists.

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Section: Compounds Fungal Sources and Biological Activitiesmentioning

confidence: 97%

Hirsutellones and beyond: figuring out the biological and synthetic logics toward chemical complexity in fungal PKS-NRPS compounds

Ear

Nay

2013

Nat. Prod. Rep.

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“…1 A). These compounds share a 13-membered para -cyclophane ether generated from l -tyrosine crosslinked to a fused [6.5.6] tricarbocyclic core and a hydroxypyrrolidinone moiety and are detected in various fungal species, such as Neonectria ramulariae 6 , 7 , Acremonium zeae 8 , Hirsutella spp 3 , 9 , Cordyceps sinensis 10 , and Penicillium spp 11 , 12 . These derivatives have potential antitumor, antifungal, antibacterial, antituberculosis, and enzyme-inhibiting activities 3 , 5 , 13 .…”

Section: Introductionmentioning

confidence: 99%

Tricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with XenF-mediated sigmatropic rearrangement as a prerequisite

Liu

Zhang

et al. 2021

Acta Pharmaceutica Sinica B

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Tyrosine-decahydrofluorene derivatives feature a fused [6.5.6] tricarbocyclic core and a 13-membered para -cyclophane ether. Herein, we identified new xenoacremones A, B, and C ( 1 − 3 ) from the fungal strain Xenoacremonium sinensis ML-31 and elucidated their biosynthetic pathway using gene deletion in the native strain and heterologous expression in Aspergillus nidulans . The hybrid polyketide synthase–nonribosomal peptide synthetase (PKS−NRPS) XenE together with enoyl reductase XenG were confirmed to be responsible for the formation of the tyrosine-nonaketide skeleton. This skeleton was subsequently dehydrated by XenA to afford a pyrrolidinone moiety. XenF catalyzed a novel sigmatropic rearrangement to yield a key cyclohexane intermediate as a prerequisite for the formation of the multi-ring system. Subsequent oxidation catalyzed by XenD supplied the substrate for XenC to link the para -cyclophane ether, which underwent subsequent spontaneous Diels−Alder reaction to give the end products. Thus, the results indicated that three novel enzymes XenF, XenD, and XenC coordinate to assemble the [6.5.6] tricarbocyclic ring and para -cyclophane ether during biosynthesis of complex tyrosine-decahydrofluorene derivatives.

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“…3 Since endophytic fungi produce characteristic compounds through the stimulation from host plants, it is suggested that endophytic fungi have a different metabolic pathway from other microorganisms. 4 Previously, we have found the novel bioactive compounds such as eremoxylarins A and B (inhibitors of Ca 2+ signal transduction), 5,6 and bispyrrocidine (inhibitor of prolyl oligopeptidase), 7 from metabolites of endophytic fungi.…”

Section: Introductionmentioning

confidence: 99%

Allantopyrone A activates Keap1–Nrf2 pathway and protects PC12 cells from oxidative stress-induced cell death

et al. 2016

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Keap1-Nrf2 system is known as a sensor of electrophilic compounds, and protects cells from oxidative stress through induction of various antioxidant enzymes. We found by proteomic analysis that allantopyrone A, a metabolite isolated from an endophytic fungus, upregulates the expression of proteins that are regulated by the transcription factor Nrf2. Indeed, allantopyrone A increased the antioxidant enzyme heme oxygenase-1 in PC12 cells. Moreover, it induced localization of Nrf2 in the nucleus. Affinity purification of allantopyrone A-binding protein showed that this compound could bind directly to Keap1. Allantopyrone A suppressed intracellular reactive oxygen species level and cell death induced by H 2 O 2 in PC12 cells. These results indicate that allantopyrone A protects PC12 cells from oxidative stress-induced cell death through direct binding with Keap1 and activation of the Keap1-Nrf2 pathway.

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A dimeric pyrrocidine from Neonectria ramulariae is an inhibitor of prolyl oligopeptidase

Cited by 18 publications

References 12 publications

Hirsutellones and beyond: figuring out the biological and synthetic logics toward chemical complexity in fungal PKS-NRPS compounds

Hirsutellones and beyond: figuring out the biological and synthetic logics toward chemical complexity in fungal PKS-NRPS compounds

Tricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with XenF-mediated sigmatropic rearrangement as a prerequisite

Allantopyrone A activates Keap1–Nrf2 pathway and protects PC12 cells from oxidative stress-induced cell death

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