Dhilirolides A−D, Meroterpenoids Produced in Culture by the Fruit-Infecting Fungus <i>Penicillium purpurogenum</i> Collected in Sri Lanka

Silva, E.Dilip de; Williams, David E.; Jayanetti, Dinith R.; Centko, Ryan M.; Patrick, Brian O.; Wijesundera, R.L.C.; Andersen, Raymond J.

doi:10.1021/ol200031t

Cited by 35 publications

(57 citation statements)

References 10 publications

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“…Compound 121 seems to 16 miniolutelides, 90,91 and dhilirolides. 92,93 The possible mechanisms for the spiro-ring formation and the cycloheptadieneformation of 121 are discussed later in this section.…”

Section: Biosyntheses Of Austinol/dehydroaustinol and Related Compoundsmentioning

confidence: 99%

Biosynthesis of fungal meroterpenoids

2016

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Covering: up to September 2015. Meroterpenoids are hybrid natural products that partially originate from the terpenoid pathway. The meroterpenoids derived from fungi display quite diverse structures, with a wide range of biological properties. This review summarizes the molecular bases for their biosyntheses, which were recently elucidated with modern techniques, and also discusses the plausible biosynthetic pathways of other related natural products lacking genetic information. (Complementary to the coverage of literature by Geris and Simpson in Nat. Prod. Rep., 2009, 26, 1063-1094.).

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Section: Biosyntheses Of Austinol/dehydroaustinol and Related Compoundsmentioning

confidence: 99%

Biosynthesis of fungal meroterpenoids

2016

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“…Several Penicillium purpurogenum strains are known to produce novel structural metabolites, including some with antitumor activities [32,33,34,35,36,37]. However, P. purpurogenum G59, a marine-derived wild type fungal strain that was initially isolated by our group [38], did not produce any metabolites with antitumor activities in an MTT assay using K562 cells [20,38].…”

Section: Introductionmentioning

confidence: 99%

A Practical Strategy to Discover New Antitumor Compounds by Activating Silent Metabolite Production in Fungi by Diethyl Sulphate Mutagenesis

Fang

Li³

et al. 2014

Marine Drugs

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Many fungal biosynthetic pathways are silent in standard culture conditions, and activation of the silent pathways may enable access to new metabolites with antitumor activities. The aim of the present study was to develop a practical strategy for microbial chemists to access silent metabolites in fungi. We demonstrated this strategy using a marine-derived fungus Penicillium purpurogenum G59 and a modified diethyl sulphate mutagenesis procedure. Using this strategy, we discovered four new antitumor compounds named penicimutanolone (1), penicimutanin A (2), penicimutanin B (3), and penicimutatin (4). Structures of the new compounds were elucidated by spectroscopic methods, especially extensive 2D NMR analysis. Antitumor activities were assayed by the MTT method using human cancer cell lines. Bioassays and HPLC-photodiode array detector (PDAD)-UV and HPLC-electron spray ionization (ESI)-MS analyses were used to estimate the activated secondary metabolite production. Compounds 2 and 3 had novel structures, and 1 was a new compound belonging to a class of very rare natural products from which only four members are so far known. Compounds 1–3 inhibited several human cancer cell lines with IC50 values lower than 20 μM, and 4 inhibited the cell lines to some extent. These results demonstrated the effectiveness of this strategy to discover new compounds by activating silent fungal metabolic pathways. These discoveries provide rationale for the increased use of chemical mutagenesis strategies in silent fungal metabolite studies.

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“…Several Penicillium purpurogenum strains are known to produce bioactive metabolites with novel structures [32,33,34,35,36], including antitumor metabolites [32]. However, Penicillium purpurogenum G59, a marine-derived wild-type strain isolated by our group, was originally not able to produce antitumor metabolites with activity in the MTT assay using K562 cells [37].…”

Section: Introductionmentioning

confidence: 99%

Purpurogemutantin and Purpurogemutantidin, New Drimenyl Cyclohexenone Derivatives Produced by a Mutant Obtained by Diethyl Sulfate Mutagenesis of a Marine-Derived Penicillium purpurogenum G59

Fang

Cui

Li³

et al. 2012

Marine Drugs

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Two new drimenyl cyclohexenone derivatives, named purpurogemutantin (1) and purpurogemutantidin (2), and the known macrophorin A (3) were isolated from a bioactive mutant BD-1-6 obtained by random diethyl sulfate (DES) mutagenesis of a marine-derived Penicillium purpurogenum G59. Structures and absolute configurations of 1 and 2 were determined by extensive spectroscopic methods, especially 2D NMR and electronic circular dichroism (ECD) analysis. Possible biosynthetic pathways for 1–3 were also proposed and discussed. Compounds 1 and 2 significantly inhibited human cancer K562, HL-60, HeLa, BGC-823 and MCF-7 cells, and compound 3 also inhibited the K562 and HL-60 cells. Both bioassay and chemical analysis (HPLC, LC-ESIMS) demonstrated that the parent strain G59 did not produce 1–3, and that DES-induced mutation(s) in the mutant BD-1-6 activated some silent biosynthetic pathways in the parent strain G59, including one set for 1–3 production.

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Dhilirolides A−D, Meroterpenoids Produced in Culture by the Fruit-Infecting Fungus Penicillium purpurogenum Collected in Sri Lanka

Cited by 35 publications

References 10 publications

Biosynthesis of fungal meroterpenoids

Biosynthesis of fungal meroterpenoids

A Practical Strategy to Discover New Antitumor Compounds by Activating Silent Metabolite Production in Fungi by Diethyl Sulphate Mutagenesis

Purpurogemutantin and Purpurogemutantidin, New Drimenyl Cyclohexenone Derivatives Produced by a Mutant Obtained by Diethyl Sulfate Mutagenesis of a Marine-Derived Penicillium purpurogenum G59

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