A Mushroom P450‐Monooxygenase Enables Regio‐ and Stereoselective Biocatalytic Synthesis of Epoxycyclohexenones

Yang, Yan‐Long; Zhou, Man; Yang, Lin; Gressler, Markus; Rassbach, Johannes; Wurlitzer, Jacob M.; Zeng, Ying; Gao, Kun; Hoffmeister, Dirk

doi:10.1002/anie.202313817

Cited by 10 publications

(2 citation statements)

References 49 publications

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“…Phylogenetically dissimilar polyketide synthases have been recognized to produce atrochrysone carboxylic acid in asco- and basidiomycetes . Likewise, ascomycetes use cupin-domain-containing enzymes to catalyze epoxidations leading to epoxycyclohexenones, while basidiomycete independently evolved cytochrome P450-dependent monooxygenases for this purpose . Our work, presented here, adds O -prenyltransfer to l -tyrosine to the repertoire of biosynthetic events that evolved along different routes in asco- and basidiomycetes.…”

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confidence: 86%

Parallel Evolution of Asco- and Basidiomycete O-Prenyltransferases

Schäfer,

Haun,

Gressler

et al. 2024

J. Nat. Prod.

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Prenyltransferases (PTs) are involved in the biosynthesis of a multitude of pharmaceutically and agriculturally important plant, bacterial, and fungal compounds. Although numerous prenylated compounds have been isolated from Basidiomycota (mushroom-forming fungi), knowledge of the PTs catalyzing the transfer reactions in this group of fungi is scarce. Here, we report the biochemical characterization of an O- and C-prenylating dimethylallyltryptophan synthase (DMATS)-like enzyme LpTyrPT from the scurfy deceiver Laccaria proxima. This PT transfers dimethylallyl moieties to l-tyrosine at the para-O position and to l-tryptophan at atom C-7 and represents the first basidiomycete l-tyrosine PT described so far. Phylogenetic analysis of PTs in fungi revealed that basidiomycete l-tyrosine PTs have evolved independently from their ascomycete counterparts and might represent the evolutionary origin of PTs acting on phenolic compounds in secondary metabolism.

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confidence: 86%

Parallel Evolution of Asco- and Basidiomycete O-Prenyltransferases

Schäfer,

Haun,

Gressler

et al. 2024

J. Nat. Prod.

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“…Agaricus macrosporus ( 46 – 54 ) and A. brasiliensis ( 58 and 60 ) are known to produce derivatives of 71 , but the genomes of these species have yet to be reported. Considering the significant relatedness among members of the Agaricus genus, we examined existing Agaricus genomes using PanA, a recently discovered PAL, as a probe. This search led to the identification of six potential PAL candidates.…”

Section: Biosynthetic Analysesmentioning

confidence: 99%

Chemical Structures, Biological Activities, and Biosynthetic Analysis of Secondary Metabolites from Agaricus Mushrooms: A Review

Zhang,

Zhao,

Tang

et al. 2024

J. Agric. Food Chem.

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Agaricus mushrooms are an important genus in the Agaricaceae family, belonging to the order Agaricales of the class Basidiomycota. Among them, Agaricus bisporus is a common mushroom for mass consumption, which is not only nutritious but also possesses significant medicinal properties such as anticancer, antibacterial, antioxidant, and immunomodulatory properties. The rare edible mushroom, Agaricus blazei, contains unique agaricol compounds with significant anticancer activity against liver cancer. Agaricus blazei is believed to expel wind and cold, i.e., the pathogenic factors of wind and cold from the body, and is an important formula in traditional Chinese medicine. Despite its nutritional richness and outstanding medicinal value, Agaricus mushrooms have not been systematically compiled and summarized. Therefore, the present review compiles and classifies 70 natural products extracted from Agaricus mushrooms over the past six decades. These compounds exhibit diverse biological and pharmacological activities, with particular emphasis on antitumor and antioxidant properties. While A. blazei and A. bisporus are the primary producers of these compounds, studies on secondary metabolites from other Agaricus species remain limited. Further research is needed to explore and understand the anticancer and nutritional properties of Agaricus mushrooms. This review contributes to the understanding of the structure, bioactivity, and biosynthetic pathways of Agaricus compounds and provides insights for the development of functional foods using these mushrooms.

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Regioselektive Oxidative Phenolkupplung durch eine Unspezifische Peroxygenase aus Ständerpilzen

Platz,

Löhr,

Girkens

et al. 2024

Angewandte Chemie

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Bioactive dimeric (pre‐)anthraquinones are ubiquitous in nature. Their biosynthesis via an oxidative phenol coupling (OPC) step is catalyzed by either cytochrome P450 enzymes, peroxidases, or laccases. While the biocatalysis of OPC in molds (Ascomycota) is well‐known, the respective enzymes of mushroom‐forming fungi (Basidiomycota) are still unknown. Here, we report on the biosynthesis of the atropisomers phlegmacin A1 and B1, unsymmetrical 7,10’‐homo‐coupled dihydroanthracenones of the mushroom Cortinarius odorifer. The biosynthesis was heterologously reconstituted in the mold Aspergillus niger. We show that methylation of the dimeric (pre‐)anthraquinone building block atrochrysone to its 6‐O‐methyl ether torosachrysone by the O‐methyltransferase (CoOMT1) precedes the regioselective homo‐coupling to phlegmacin, catalyzed by an unspecific peroxygenase (CoUPO1). Our results revealed an unprecedented UPO‐mediated unsymmetric OPC reaction, thereby expanding the biocatalytic portfolio of OPC‐type reactions beyond the commonly reported enzymes. The findings highlight the pivotal role of OPC in natural processes, demonstrating that Basidiomycota employed peroxygenases to develop the ability to selectively couple aryls, distinct and convergent to any other group of organisms.

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A Mushroom P450‐Monooxygenase Enables Regio‐ and Stereoselective Biocatalytic Synthesis of Epoxycyclohexenones

Cited by 10 publications

References 49 publications

Parallel Evolution of Asco- and Basidiomycete O-Prenyltransferases

Parallel Evolution of Asco- and Basidiomycete O-Prenyltransferases

Chemical Structures, Biological Activities, and Biosynthetic Analysis of Secondary Metabolites from Agaricus Mushrooms: A Review

Regioselektive Oxidative Phenolkupplung durch eine Unspezifische Peroxygenase aus Ständerpilzen

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