Unprecedented [5.5.5.6]Dioxafenestrane Ring Construction in Fungal Insecticidal Sesquiterpene Biosynthesis

Zeng, Haichun; Yin, Guoping; Qian, Wei; Li, Dehai; Wang, Yi; Hu, Youcai; Hu, Changhua; Zou, Yi

doi:10.1002/ange.201813722

Cited by 7 publications

(2 citation statements)

References 37 publications

(75 reference statements)

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“…In our continuous studies on discovering enzymes for the cleavage of prenyl chains in natural product biosyntheses21, 22, we have focused on 1 using an MPA high-producing strain Penicillium griseofulvum (Supporting Information Fig. S1)23, 24. The strain provides a convenient platform for analyzing accumulated intermediates produced by gene mutants.…”

Section: Resultsmentioning

confidence: 99%

Immunosuppressant mycophenolic acid biosynthesis employs a new globin-like enzyme for prenyl side chain cleavage

Chen

Wang

Zhang

et al. 2019

Acta Pharmaceutica Sinica B

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Mycophenolic acid (MPA, 1) and its derivatives are first-line immunosuppressants used in organ transplantation and for treating autoimmune diseases. Despite chemical synthetic achievements, the biosynthetic formation of a seven-carbon carboxylic acid pharmacophore side chain of 1, especially the processes involving the cleavage of the prenyl side chain between DHMP (4) and DMMPA (5), remains unknown. In this work, we identified a membrane-bound prenyltransferase, PgMpaA, that transfers FPP to 4 to yield FDHMP (6). Compound 6 undergoes the first cleavage step via a new globin-like enzyme PgMpaB to form a cryptic intermediate 12. Heterologous expression of PgMpa genes in Aspergillus nidulans demonstrates that the second cleavage step (from 12 to 5) of 1 is a PgMpa cluster-independent process in vivo. Our results, especially the discovery of the broad tolerance of substrates recognized by PgMpaB, set up a strategy for the formation of “pseudo-isopentenyl” natural products using fungal globin-like enzymes.

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Section: Resultsmentioning

confidence: 99%

Immunosuppressant mycophenolic acid biosynthesis employs a new globin-like enzyme for prenyl side chain cleavage

Chen

Wang

Zhang

et al. 2019

Acta Pharmaceutica Sinica B

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“…The dioxafenestrane sesquiterpenoid pathways provide another example in which fungal sesquiterpenoids are generated in branching pathways (Fig. 6) [63,64]. The biosyntheses of penifulvins and asperaculins both begin with the cyclization of FPP into the sesquiterpene silphinene (59), which is synthesized by the terpene cyclase PeniA/AspeG.…”

Section: Dioxafenestrane Sesquiterpenoidsmentioning

confidence: 99%

Branching and converging pathways in fungal natural product biosynthesis

Wei

Wang

Matsuda

2022

Fungal Biol Biotechnol

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In nature, organic molecules with great structural diversity and complexity are synthesized by utilizing a relatively small number of starting materials. A synthetic strategy adopted by nature is pathway branching, in which a common biosynthetic intermediate is transformed into different end products. A natural product can also be synthesized by the fusion of two or more precursors generated from separate metabolic pathways. This review article summarizes several representative branching and converging pathways in fungal natural product biosynthesis to illuminate how fungi are capable of synthesizing a diverse array of natural products.

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Biosynthesis of Sordarin Revealing a Diels–Alderase for the Formation of the Norbornene Skeleton

Liu

Sun

et al. 2022

Angewandte Chemie

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Sordarin (1) is a fungal diterpene glycoside that displays potent antifungal bioactivity through inhibition of elongation factor 2. The structures of sordarin and related compounds feature a highly rearranged tetracyclic diterpene core. In this study, we identified a concise pathway in the biosynthesis of sordarin. A diterpene cyclase (SdnA) generates the 5/8/5 cycloaraneosene framework, which is decorated by a set of P450s that catalyze a series of oxidation reactions, including hydroxylation, desaturation, and C−C bond oxidative cleavage, to give a carboxylate intermediate with a terminal alkene and a cyclopentadiene moiety. A novel Diels–Alderase SdnG catalyzes an intramolecular Diels–Alder (IMDA) reaction on this intermediate to forge the sordarin core structure. Subsequent methyl hydroxylation and glycosylation complete the biosynthesis of sordarin. Our work discloses a new strategy used by nature for the formation of the rearranged diterpene skeleton.

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Unprecedented [5.5.5.6]Dioxafenestrane Ring Construction in Fungal Insecticidal Sesquiterpene Biosynthesis

Cited by 7 publications

References 37 publications

Immunosuppressant mycophenolic acid biosynthesis employs a new globin-like enzyme for prenyl side chain cleavage

Immunosuppressant mycophenolic acid biosynthesis employs a new globin-like enzyme for prenyl side chain cleavage

Branching and converging pathways in fungal natural product biosynthesis

Biosynthesis of Sordarin Revealing a Diels–Alderase for the Formation of the Norbornene Skeleton

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