Tremorgenic mycotoxins from Penicillium crustosum. Structure elucidation and absolute configuration of penitrems B–F

Jesus, Amelia E. de; Steyn, Pieter S.; Heerden, Fanie R. van; Vleggaar, Robert; Wessels, Philippus L.; Hull, William E.

doi:10.1039/p19830001857

Cited by 45 publications

(38 citation statements)

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“…[5,6] These metabolites have ac ommon hexacyclic core structure,w hich is frequently modified by prenylation, aside from further modifications that give carbocycles and cyclic ethers (Figure 1). [9] Among these strains, P. crustosum produces the penitrem homologues A-F [7] and paxilline-related metabolites,such as paspaline (3), [10] PC-M5 (4), and PC-M4 [11] (5;S cheme 1). [9] Among these strains, P. crustosum produces the penitrem homologues A-F [7] and paxilline-related metabolites,such as paspaline (3), [10] PC-M5 (4), and PC-M4 [11] (5;S cheme 1).…”

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confidence: 99%

Reconstitution of Biosynthetic Machinery for the Synthesis of the Highly Elaborated Indole Diterpene Penitrem

et al. 2015

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Penitrem A is one of the most elaborated members of the fungal indole diterpenes. Two separate penitrem gene clusters were identified using genomic and RNA sequencing data, and 13 out of 17 transformations in the penitrem biosynthesis were elucidated by heterologous reconstitution of the relevant genes. These reactions involve 1) a prenylation-initiated cationic cyclization to install the bicyclo[3.2.0]heptane skeleton (PtmE), 2) a two-step P450-catalyzed oxidative processes forming the unique tricyclic penitrem skeleton (PtmK and PtmU), and 3) five sequential oxidative transformations (PtmKULNJ). Importantly, without conventional gene disruption, reconstitution of the biosynthetic machinery provided sufficient data to determine the pathway. It was thus demonstrated that the Aspergillus oryzae reconstitution system is a powerful method for studying the biosynthesis of complex natural products.

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Reconstitution of Biosynthetic Machinery for the Synthesis of the Highly Elaborated Indole Diterpene Penitrem

et al. 2015

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“…SI1 and SI2 in Supplementary Information) afforded the known indole diterpene alkaloids penitrems A, B, D, E, and F ( 1 – 5 ) and their biosynthetic precursors paspaline ( 6 ) and emindole SB ( 7 ). 16,17 …”

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Bioguided discovery and pharmacophore modeling of the mycotoxic indole diterpene alkaloids penitrems as breast cancer proliferation, migration, and invasion inhibitors

et al. 2013

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Marine-derived fungi have proven to be important sources of bioactive natural organohalides. The genus Penicillium is recognized as a rich source of chemically diverse bioactive secondary metabolites. This study reports the fermentation, isolation and identification of a marine-derived Penicillium species. Bioassay-guided fractionation afforded the indole diterpene alkaloids penitrems A, B, D, E and F as well as paspaline and emnidole SB (1–7). Supplementing the fermentation broth of the growing fungus with KBr afforded the new 6-bromopenitrem B (8) and the known 6-bromopenitrem E (9). These compounds showed good antiproliferative, antimigratory and anti-invasive properties against human breast cancer cells. Penitrem B also showed a good activity profile in the NCI-60 DTP human tumor cell line screen. The nematode Caenorhabditis elegans was used to assess the BK channel inhibitory activity and toxicity of select compounds. A pharmacophore model was generated to explain the structural relationships of 1–9 with respect to their antiproliferative activity against the breast cancer MCF-7 cells. The structurally less complex biosynthetic precursors, paspaline (6) and emindole SB (7), were identified as potential hits suitable for future studies.

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“…14, 15 Further comparison with literature reports suggested that compound 1 was an indole-diterpene derivative related to penitrem A (9), which was isolated from the culture of Penicillium crustosum.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…In addition to rhizovarins A−F (1−6), 14 known indolediterpenes, including secopenitrem D (7), 27 PC-M4 (8), 30 penitrems A−F (9−14), 15 33 3-deoxo-4b-deoxypaxilline (19), 34 and 3b-hydroxy4b-desoxypaxilline (20), 35 were also isolated and identified. The structures of these compounds were determined by spectroscopic analysis.…”

Section: Journal Of Natural Productsmentioning

confidence: 99%

“…The relative configuration for the stereogenic centers of 4 was determined to be the same as that of known diterpenes penitrems A−F by NOESY experiments. 15 The molecular formula of compound 5 was determined as C 38 H 49 NO 6 by HRESIMS data. The structure elucidation of 5 was straightforward due to its close relationship to the reported indole-diterpene secopenitrem D (7), 27 which was isolated from a strain of P. crustosum Thom.…”

Section: Journal Of Natural Productsmentioning

confidence: 99%

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Rhizovarins A–F, Indole-Diterpenes from the Mangrove-Derived Endophytic Fungus Mucor irregularis QEN-189

Gao

Williams

et al. 2016

J. Nat. Prod.

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Genome mining of the fungus Mucor irregularis (formerly known as Rhizomucor variabilis) revealed the presence of various gene clusters for secondary metabolite biosynthesis, including several terpene-based clusters. Investigation into the chemical diversity of M. irregularis QEN-189, an endophytic fungus isolated from the fresh inner tissue of the marine mangrove plant Rhizophora stylosa, resulted in the discovery of 20 structurally diverse indole-diterpenes including six new compounds, namely, rhizovarins A−F (1−6). Among them, compounds 1−3 represent the most complex members of the reported indole-diterpenes. The presence of an unusual acetal linked to a hemiketal (1) or a ketal (2 and 3) in an unprecedented 4,6,6,8,5,6,6,6,6-fused indole-diterpene ring system makes them chemically unique. Their structures and absolute configurations were elucidated by spectroscopic analysis, modified Mosher's method, and chemical calculations. Each of the isolated compounds was evaluated for antitumor activity against HL-60 and A-549 cell lines.

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Tremorgenic mycotoxins from Penicillium crustosum. Structure elucidation and absolute configuration of penitrems B–F

Cited by 45 publications

References 2 publications

Reconstitution of Biosynthetic Machinery for the Synthesis of the Highly Elaborated Indole Diterpene Penitrem

Reconstitution of Biosynthetic Machinery for the Synthesis of the Highly Elaborated Indole Diterpene Penitrem

Bioguided discovery and pharmacophore modeling of the mycotoxic indole diterpene alkaloids penitrems as breast cancer proliferation, migration, and invasion inhibitors

Rhizovarins A–F, Indole-Diterpenes from the Mangrove-Derived Endophytic Fungus Mucor irregularis QEN-189

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