The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. V. Minor metabolites.

Blows, William M.; Foster, Graham; Lane, Stephen; Noble, David; Piercey, J.E.; Sidebottom, Philip J.; Webb, G. A.

doi:10.7164/antibiotics.47.740

Cited by 46 publications

(24 citation statements)

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“…Squalestatin 1 exhibits broad-spectrum antifungal activity [ 64 ] and was identified in Phoma sp. and several ascomycetes [ 65 , 66 ]. AbT1 (100% similarity) is a precursor of the cyclic peptide antibiotic Aureobasidin A (AbA), known to be produced by Aureobasidium pullulans [ 67 ].…”

Section: Resultsmentioning

confidence: 99%

Genome Sequencing of Paecilomyces Penicillatus Provides Insights into Its Phylogenetic Placement and Mycoparasitism Mechanisms on Morel Mushrooms

et al. 2020

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Morels (Morchella spp.) are popular edible fungi with significant economic and scientific value. However, white mold disease, caused by Paecilomyces penicillatus, can reduce morel yield by up to 80% in the main cultivation area in China. Paecilomyces is a polyphyletic genus and the exact phylogenetic placement of P. penicillatus is currently still unclear. Here, we obtained the first high-quality genome sequence of P. penicillatus generated through the single-molecule real-time (SMRT) sequencing platform. The assembled draft genome of P. penicillatus was 40.2 Mb, had an N50 value of 2.6 Mb and encoded 9454 genes. Phylogenetic analysis of single-copy orthologous genes revealed that P. penicillatus is in Hypocreales and closely related to Hypocreaceae, which includes several genera exhibiting a mycoparasitic lifestyle. CAZymes analysis demonstrated that P. penicillatus encodes a large number of fungal cell wall degradation enzymes. We identified many gene clusters involved in the production of secondary metabolites known to exhibit antifungal, antibacterial, or insecticidal activities. We further demonstrated through dual culture assays that P. penicillatus secretes certain soluble compounds that are inhibitory to the mycelial growth of Morchella sextelata. This study provides insights into the correct phylogenetic placement of P. penicillatus and the molecular mechanisms that underlie P. penicillatus pathogenesis.

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Section: Resultsmentioning

confidence: 99%

Genome Sequencing of Paecilomyces Penicillatus Provides Insights into Its Phylogenetic Placement and Mycoparasitism Mechanisms on Morel Mushrooms

et al. 2020

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“…C2932. These were later followed by 19 other squalestatins differing by the structure of O-acyl radicals and bicyclooctane nucleus [83].…”

Section: Antibiotics Inhibiting the Late Stages Of Cholesterol Biosynmentioning

confidence: 99%

Antibiotics inhibiting the biosynthesis of cholesterol (a review)

Тренин

Катруха

1997

Pharm Chem J

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The several decades that have passed since the introduction of penicillin into medical practice is essentially the age of antibiotics. Their wide application was very fruitful and allowed the solution of a number of fundamental problems both in the field of infection pathology and in treating diseases of a non-infection nature [ 1,2]. As is well known, antibiotics are not only successfully used as antimicrobial preparations, but are also applied in oncology as antitumor drugs. Moreover, it was the discovery of microbial metabolites-immunomodulators and the creation of immunodepressants such as eyclosporin A and FK 506 that made possible surgical operations involving the transplantation of organs and tissues [3 -5].

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“…The triacid 1 was the first natural product found to be a potent inhibitor of squalene synthase and it also exhibited broad-spectrum antifungal activity. Because of its extraordinary potency, the triacid 1 and structurally related congeners such as 6,7-dideoxysqualestatin H5 (DDSQ, 2) 7 represented exciting new therapeutic leads in the treatment of DDSQ (2) In the summer of 1993, with the support of a Nuffield Foundation undergraduate research bursary award, Vittorio Caprio (now at Manchester Metropolitan University) found that a glyoxylate can function as a dipolarophile with a carbonyl ylide and that it reacted with the desired regiochemistry, but undesired exo/endo stereochemistry. Nevertheless, this preliminary result assisted a research grant application to the UK Science and Engineering Research Council (SERC), which was assessed by an organic chemistry subcommittee who could recommend earmarked studentships to the chemistry committee ( Figure 2).…”

Section: Introductionmentioning

confidence: 99%

Evolution of a Cycloaddition–Rearrangement Approach to the Squalestatins: A Quarter-Century Odyssey

Almohseni¹,

Hodgson

2020

Synlett

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The highs, lows, and diversions of a journey leading to two syntheses of 6,7-dideoxysqualestatin H5 is described. Both syntheses relied on highly diastereoselective n-alkylations of a tartrate acetonide enolate and subsequent oxidation–hydrolysis to provide an asymmetric entry to β-hydroxy-α-ketoester motifs. The latter were differentially elaborated to diazoketones which underwent stereo- and regioselective Rh(II)-catalysed cyclic carbonyl ylide formation–cycloaddition and then acid-catalysed transketalisation to generate the 2,8-dioxabicyclo[3.2.1]octane core of the squalestatins/zaragozic acids at the correct tricarboxylate oxidation level. The unsaturated side chain was either protected with a bromide substituent during the transketalisation or introduced afterwards by a stereoretentive Ni-catalyzed Csp3–Csp2 cross-electrophile coupling.1 Introduction 2 Racemic Model Studies to the Squalestatin/Zaragozic Acid Core3 Asymmetric Model Studies to a Keto α-Diazoester3.1 Dialkyl Squarate Desymmetrisation3.2 Tartrate Alkylation3.2.1 Further Studies on Seebach’s Alkylation Chemistry 4 Failure at the Penultimate Step to DDSQ 5 Second-Generation Approach to DDSQ: A Bromide Substituent Strategy 5.1 Stereoselective Routes to E-Alkenyl Halides via β-Oxido Phosphonium Ylides 5.2 Back to DDSQ Synthesis6 An Alternative Strategy to DDSQ: By Cross-Electrophile Coupling7 Alkene Ozonolysis in the Presence of Diazo Functionality: Accessing α-Ketoester Intermediates8 Summary

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The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. V. Minor metabolites.

Abstract: The isolation and structure determination by 1H and 1 3C NMRand MSof24 novel squalestatins from cultures of Phoma sp. C2932 is described.

Cited by 46 publications

References 0 publications

Genome Sequencing of Paecilomyces Penicillatus Provides Insights into Its Phylogenetic Placement and Mycoparasitism Mechanisms on Morel Mushrooms

Genome Sequencing of Paecilomyces Penicillatus Provides Insights into Its Phylogenetic Placement and Mycoparasitism Mechanisms on Morel Mushrooms

Antibiotics inhibiting the biosynthesis of cholesterol (a review)

Evolution of a Cycloaddition–Rearrangement Approach to the Squalestatins: A Quarter-Century Odyssey

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