6-Farnesyl-5,7-dihydroxy-4-methylphthalide oxidation mechanism in mycophenolic acid biosynthesis

Colombo, Lino; Gennari, Cesare; Potenza, Donatella; Scolastico, Carlo; Aragozzini, Fabrizio; Gualandris, Roberto

doi:10.1039/p19820000365

Cited by 23 publications

(24 citation statements)

References 7 publications

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“…The mechanism has been reported to include epoxidation of the double bond, followed by hydrolysis, rearrangement to a ketone, ␣-hydroxylation, and Woodward reaction of the ␣-hydroxyketone with C-C bond cleavage and formation of the acid (13). It is uncertain which enzyme in the gene cluster could catalyze this reaction, but MpaH has similarity to Akt2, which is involved in AK toxin biosynthesis in Alternaria alternata.…”

Section: Discussionmentioning

confidence: 99%

Molecular Basis for Mycophenolic Acid Biosynthesis in Penicillium brevicompactum

Regueira

Kildegaard

Hansen

et al. 2011

Appl Environ Microbiol

139

123

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Mycophenolic acid (MPA) is the active ingredient in the increasingly important immunosuppressive pharmaceuticals CellCept (Roche) and Myfortic (Novartis). Despite the long history of MPA, the molecular basis for its biosynthesis has remained enigmatic. Here we report the discovery of a polyketide synthase (PKS), MpaC, which we successfully characterized and identified as responsible for MPA production in Penicillium brevicompactum. mpaC resides in what most likely is a 25-kb gene cluster in the genome of Penicillium brevicompactum. The gene cluster was successfully localized by targeting putative resistance genes, in this case an additional copy of the gene encoding IMP dehydrogenase (IMPDH). We report the cloning, sequencing, and the functional characterization of the MPA biosynthesis gene cluster by deletion of the polyketide synthase gene mpaC of P. brevicompactum and bioinformatic analyses. As expected, the gene deletion completely abolished MPA production as well as production of several other metabolites derived from the MPA biosynthesis pathway of P. brevicompactum. Our work sets the stage for engineering the production of MPA and analogues through metabolic engineering.

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Section: Discussionmentioning

confidence: 99%

Molecular Basis for Mycophenolic Acid Biosynthesis in Penicillium brevicompactum

Regueira

Kildegaard

Hansen

et al. 2011

Appl Environ Microbiol

139

123

View full text Add to dashboard Cite

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“…37 An isotope-feeding study suggested the mechanism for the oxidative cleavage, in which the olen of 53 is transformed into the epoxide 55, the ketone 56, and the a-hydroxy ketone 57 in this order. 42 Subsequent C-C bond cleavage would nally produce 54, but the actual intermediates for this conversion have yet to be identied.…”

Section: Biosynthesis Of Mycophenolic Acidmentioning

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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“…In this context it is also worthwhile mentioning that 3 is reminiscent of mycophenolic acid, which results from aryl prenylation in lieu of hydroxylation. [29] For the biosynthesis of 1, two general pathways are now conceivable. A common precursor of 1-3 could be 6 that might be further elongated by three repetitive Claisen condensations.…”

Section: Resultsmentioning

confidence: 99%

Epicoccalone, a Coumarin‐Type Chymotrypsin Inhibitor, and Isobenzofuran Congeners from an Epicoccum sp. Associated with a Tree Fungus

2008

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The bioactivity‐guided fractionation of metabolites from an Epicoccum sp. isolated from the fruiting body of the tree fungus Pholiota squarrosa led to the discovery of a new inhibitor of the serine protease α‐chymotrypsin. The structure of the active compound, epicoccalone (1), was fully elucidated by spectrometric and spectroscopic methods, revealing a coumarin ring system with an unprecedented substitution pattern. Two isobenzofuran‐derived co‐metabolites were identified that are remarkably similar to the epicoccalone coumarin core, strongly suggesting that these metabolites share the same orsellinic acid like polyketide pathway.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

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6-Farnesyl-5,7-dihydroxy-4-methylphthalide oxidation mechanism in mycophenolic acid biosynthesis

Cited by 23 publications

References 7 publications

Molecular Basis for Mycophenolic Acid Biosynthesis in Penicillium brevicompactum

Molecular Basis for Mycophenolic Acid Biosynthesis in Penicillium brevicompactum

Biosynthesis of fungal meroterpenoids

Epicoccalone, a Coumarin‐Type Chymotrypsin Inhibitor, and Isobenzofuran Congeners from an Epicoccum sp. Associated with a Tree Fungus

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