Pseurotin, a New Metabolite of <i>Pseudeurotium ovalis</i> S<scp>TOLK</scp> Having an Unusual Hetero‐Spirocyclic System. (Preliminary Communication)

Bloch, Peter; Tamm, Christoph; Bollinger, Pietro; Petcher, Trevor J.; Weber, Hans Peter

doi:10.1002/hlca.19760590114

Cited by 110 publications

(66 citation statements)

References 11 publications

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“…Pseurotin A, first isolated from Pseudoeurotium ovalis [11] is a competitive inhibitor of chitin synthase, [14] and a neuritogenic agent. [23] Feeding experiments showed that pseurotin A is derived from one molecule of propionyl-coenzyme A, one molecule of phenylalanine and four molecules of malonyl-coen-A C H T U N G T R E N N U N G zyme A.…”

Section: Discussionmentioning

confidence: 99%

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Identification of a Hybrid PKS/NRPS Required for Pseurotin A Biosynthesis in the Human Pathogen Aspergillus fumigatus

et al. 2007

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The genome sequence of Aspergillus fumigatus revealed the presence of a single hybrid polyketide synthase-non-ribosomal peptide synthetase (PKS/NRPS) gene that is present within a cluster of five genes suggestive of its involvement in secondary metabolism. Here, we present evidence that it is required for the biosynthesis of pseurotin A, a compound with an unusual heterospirocyclic gamma-lactam structure. We have confirmed that the genome reference strain A. fumigatus Af293 produces pseurotin A, a compound previously reported to be a competitive inhibitor of chitin synthase and an inducer of nerve-cell proliferation. Deletion or overexpression of the PKS/NRPS gene psoA in A. fumigatus leads to the absence or accumulation of pseurotin A, respectively; this indicates that this gene is essential for the biosynthesis of pseurotin A. It is likely that the first product of psoA is converted to pseurotin A by the products of other genes in this cluster.

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Section: Discussionmentioning

confidence: 99%

“…[11] Together with 8-O-demethylpseurotin A (2) and synerazol (3), it was also isolated from A. fumigatus. [12,13,14] Azaspirene (4), with the same core structure, was obtained from A C H T U N G T R E N N U N G Neosartorya sp.…”

Section: Bioinformaticsmentioning

confidence: 99%

Identification of a Hybrid PKS/NRPS Required for Pseurotin A Biosynthesis in the Human Pathogen Aspergillus fumigatus

et al. 2007

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“…-The pseurotins are a small family of secondary microbial metabolites which have been isolated from cultures of Pseudeurotium ovalis STOLK. The isolation, spectral data, and chemical properties as well as biosynthetic studies on the main component, pseurotin A (l), have been already reported [2]. Pseurotin A (1) possesses a novel highly substituted l-oxa-7-azaspiro [4.4]nonane skeleton and five chiral centers.…”

Section: Synthetic Studies Towards Pseurotinmentioning

confidence: 98%

Synthetic Studies towards Pseurotin A. Part 3. Synthesis of a related highly functionalized γ‐lactone

Tamm

1995

Helvetica Chimica Acta

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Dedicated to Albert Eschenmoser on the occasion of his 70th birthday ( 2 8 . N . 95) A new general concept for the total synthesis of pseurotin A (l), a secondary metabolite of Pseudeurotium ovalis STOLK, which possesses a highly substituted 1 -oxa-7-azaspiro[4.4]nonane skeleton, is presented. A key intermediate of the planned reaction sequence is the functionalized y-lactone 8. The corresponding protected compound 52 was prepared using (S)-0,O-isopropylideneglyceraldehyde (13) and the bromoacetall4 as starting material. y-Lactone 52 was obtained in enantiomerically pure state in ten steps. It possesses the desired configuration.

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“…[66][67][68][69] Genome sequencing of Aspergillus fumigatus 70) has revealed a number of gene clusters that are predicted to encode for enzymes that constitute natural product biosynthetic pathways. The gene cluster responsible for the biosynthesis of pseurotin A (19) was predicted and identified by deleting or overexpressing a PKS-NRPS gene psoA in A. fumigatus Af293 71) (Table 1).…”

Section: Understanding Pseurotin Scaffold By Functional Analysis Of Tmentioning

confidence: 99%

Effective Use of Heterologous Hosts for Characterization of Biosynthetic Enzymes Allows Production of Natural Products and Promotes New Natural Product Discovery

Watanabe

2014

CHEMICAL & PHARMACEUTICAL BULLETIN

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In the past few years, there has been impressive progress in elucidating the mechanism of biosynthesis of various natural products accomplished through the use of genetic, molecular biological and biochemical techniques. Here, we present a comprehensive overview of the current results from our studies on fungal natural product biosynthetic enzymes, including nonribosomal peptide synthetase and polyketide synthasenonribosomal peptide synthetase hybrid synthetase, as well as auxiliary enzymes, such as methyltransferases and oxygenases. Specifically, biosynthesis of the following compounds is described in detail: (i) Sch210972, potentially involving a Diels-Alder reaction that may be catalyzed by CghA, a functionally unknown protein identified by targeted gene disruption in the wild type fungus; (ii) chaetoglobosin A, formed via multi-step oxidations catalyzed by three redox enzymes, one flavin-containing monooxygenase and two cytochrome P450 oxygenases as characterized by in vivo biotransformation of relevant intermediates in our engineered Saccharomyces cerevisiae; (iii) ( )-ditryptophenaline, formed by a cytochrome P450, revealing the dimerization mechanism for the biosynthesis of diketopiperazine alkaloids; (iv) pseurotins, whose variations in the Cand O-methylations and the degree of oxidation are introduced combinatorially by multiple redox enzymes; and (v) spirotryprostatins, whose spiro-carbon moiety is formed by a flavin-containing monooxygenase or a cytochrome P450 as determined by heterologous de novo production of the biosynthetic intermediates and final products in Aspergillus niger. We close our discussion by summarizing some of the key techniques that have facilitated the discovery of new natural products, production of their analogs and identification of biosynthetic mechanisms in our study.

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Pseurotin, a New Metabolite of Pseudeurotium ovalis STOLK Having an Unusual Hetero‐Spirocyclic System. (Preliminary Communication)

Cited by 110 publications

References 11 publications

Identification of a Hybrid PKS/NRPS Required for Pseurotin A Biosynthesis in the Human Pathogen Aspergillus fumigatus

Identification of a Hybrid PKS/NRPS Required for Pseurotin A Biosynthesis in the Human Pathogen Aspergillus fumigatus

Synthetic Studies towards Pseurotin A. Part 3. Synthesis of a related highly functionalized γ‐lactone

Effective Use of Heterologous Hosts for Characterization of Biosynthetic Enzymes Allows Production of Natural Products and Promotes New Natural Product Discovery

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