Biosynthesis of Griseofulvin. Observations on the Incorporation of [14c]griseophenone C and [36ci]griseophenones B and A

Rhodes, Andrea L.; Somerfield, G. A.; McGonagle, Moira P.

doi:10.1042/bj0880349

Cited by 20 publications

(16 citation statements)

References 7 publications

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“…Taken together, these studies with MTs confirm that the GsfA product undergoes methylation by both GsfB and GsfC before forming the grisan ring, which is in agreement of the previous feeding studies. 14, 15 …”

Section: Resultsmentioning

confidence: 99%

Complexity Generation in Fungal Polyketide Biosynthesis: A Spirocycle-Forming P450 in the Concise Pathway to the Antifungal Drug Griseofulvin

et al. 2013

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Griseofulvin (1) is a spirocyclic fungal natural product used in treatment of fungal dermatophytes. Formation of the spirocycle, or the grisan scaffold, from a benzophenone precursor is critical for the activity of 1. In this study, we have systematically characterized each of the biosynthetic enzymes related to the biogenesis of 1, including the characterization of a new polyketide synthase GsfA that synthesize the benzophenone precursor and a cytochrome P450 GsfF that performs oxidative coupling between the orcinol and the phloroglucinol rings to yield the grisan structure. Notably, the finding of GsfF is in sharp contrast to the copper-dependent dihydrogeodin oxidase that performs a similar reaction in the geodin biosynthetic pathway. The biosynthetic knowledge enabled the in vitro total biosynthesis of 1 from malonyl-CoA using all purified enzyme components. This work therefore completely maps out the previously unresolved enzymology of the biosynthesis of a therapeutically relevant natural product

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Section: Resultsmentioning

confidence: 99%

Complexity Generation in Fungal Polyketide Biosynthesis: A Spirocycle-Forming P450 in the Concise Pathway to the Antifungal Drug Griseofulvin

et al. 2013

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“…A stereospecific oxidative coupling reaction was proposed for the formation of the grisan structure of 2 (Barton and Cohen, 1957). The biosynthetic pathway of 2 has been extensively studied using isotopic incorporation (Harris et al, 1976; Lane et al, 1982; Rhodes et al, 1963; Simpson and Holker, 1977), but the genes and enzymes involved in the biosynthesis remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Identification of the Viridicatumtoxin and Griseofulvin Gene Clusters from Penicillium aethiopicum

Chooi

Cacho

Tang

2010

Chemistry & Biology

163

201

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SUMMARY Penicillium aethiopicum produces two structurally interesting and biologically active polyketides: the tetracycline-like viridicatumtoxin 1 and the classic antifungal agent griseofulvin 2. Here, we report the concurrent discovery of the two corresponding biosynthetic gene clusters (vrt and gsf) by 454 shotgun sequencing. Gene deletions confirmed two nonreducing PKSs (NRPKS), vrtA and gsfA, are required for the biosynthesis of 1 and 2, respectively. Both PKSs share similar domain architectures and lack a C-terminal thioesterase domain. We identified gsfI as the chlorinase involved in the biosynthesis of 2, as deletion of gsfI resulted in the accumulation of decholorogriseofulvin 3. Comparative analysis with the P. chrysogenum genome revealed that both clusters are embedded within conserved syntenic regions of P. aethiopicum chromosomes. Discovery of the vrt and gsf clusters provided the basis for genetic and biochemical studies of the pathways.

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“…While some fungal xanthones are produced via simple folding of a polyketide chain, e.g. norlichexanthone 5 from Lecanora straminea ,7 most are produced via Baeyer–Villiger-type oxidation of anthraquinones such as chrysophanol 6 to give benzophenones such as monodictyphenone 7 which are subsequently cyclized to xanthones 8. Recent interest in these pathways has been stimulated by the results of genome sequencing and bioinformatic analysis9 which has allowed identification of the gene clusters in, e.g.…”

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confidence: 99%

Characterisation of the biosynthetic pathway to agnestins A and B reveals the reductive route to chrysophanol in fungi

et al. 2019

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Biosynthesis of Griseofulvin. Observations on the Incorporation of [14c]griseophenone C and [36ci]griseophenones B and A

Cited by 20 publications

References 7 publications

Complexity Generation in Fungal Polyketide Biosynthesis: A Spirocycle-Forming P450 in the Concise Pathway to the Antifungal Drug Griseofulvin

Complexity Generation in Fungal Polyketide Biosynthesis: A Spirocycle-Forming P450 in the Concise Pathway to the Antifungal Drug Griseofulvin

Identification of the Viridicatumtoxin and Griseofulvin Gene Clusters from Penicillium aethiopicum

Characterisation of the biosynthetic pathway to agnestins A and B reveals the reductive route to chrysophanol in fungi

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