Biosynthesis of fungal terpenoids

Natural Product Reports, Год журнала: 2024, Номер 41(5), С. 748 - 783

Опубликована: Янв. 1, 2024

This review covers all fungal terpenoid cyclases (TCs), including class I and II TCs as well emerging UbiA-type TCs, together with their tailoring enzymes, focusing on newly identified enzymes from 2015 to August 2023.

Язык: Английский

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The chemistry and biology of fungal meroterpenoids (2009–2019)

Organic & Biomolecular Chemistry, Год журнала: 2020, Номер 19(8), С. 1644 - 1704

Опубликована: Дек. 10, 2020

Fungal meroterpenoids are secondary metabolites from mixed terpene-biosynthetic origins. Their intriguing chemical structural diversification and complexity, potential bioactivities, pharmacological significance make them attractive targets in natural product chemistry, organic synthesis, biosynthesis. This review provides a systematic overview of the isolation, features, biological activities, fungal biodiversity 1585 novel 79 genera terrestrial marine-derived fungi including macrofungi, Basidiomycetes, 441 research papers 2009-2019. Based on nonterpenoid starting moiety their biosynthesis pathway, were classified into four categories (polyketide-terpenoid, indole-, shikimate-, miscellaneous-) with polyketide-terpenoids (mainly tetraketide-) shikimate-terpenoids as primary source. Basidiomycota produced 37.5% meroterpenoids, mostly shikimate-terpenoids. The Ganoderma, Penicillium, Aspergillus, Stachybotrys dominant producers. Moreover, about 56% display various pronounced cytotoxicity, enzyme inhibition, antibacterial, anti-inflammatory, antiviral, antifungal activities. It's exciting that several antroquinonol 4-acetyl B developed phase II clinically used drugs. We assume diversity therapeutic these will provide biologists medicinal chemists large promising sustainable treasure-trove for drug discovery.

Язык: Английский

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Structural diversity, hypothetical biosynthesis, chemical synthesis, and biological activity ofGanodermameroterpenoids

Natural Product Reports, Год журнала: 2023, Номер 40(8), С. 1354 - 1392

Опубликована: Янв. 1, 2023

This review comprehensively summaries the structure diversity and possible biosynthesis of representative Ganoderma meroterpenoids (GMs), as well chemical synthesis pharmacological activities some significant GMs.

Язык: Английский

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Class II terpene cyclases: structures, mechanisms, and engineering

Natural Product Reports, Год журнала: 2023, Номер 41(3), С. 402 - 433

Опубликована: Дек. 18, 2023

This review offers an overview of the canonical and noncanonical class II terpene cyclases, including sesquiterpene, diterpene, triterpene, meroterpenoid cyclases. It delves into their sequences, structures, mechanisms, engineering studies.

Язык: Английский

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Discovery of fungal onoceroid triterpenoids through domainless enzyme-targeted global genome mining

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 21, 2024

Abstract Genomics-guided methodologies have revolutionized the discovery of natural products. However, a major challenge in field genome mining is determining how to selectively extract biosynthetic gene clusters (BGCs) for untapped products from numerous available sequences. In this study, we developed fungal tool that extracts BGCs encoding enzymes lack detectable protein domain (i.e., domainless enzymes) and are not recognized as proteins by existing bioinformatic tools. We searched homologue Pyr4-family terpene cyclases, which representative examples apparently enzymes, approximately 2000 genomes discovered several with unique features. The subsequent characterization selected led onoceroid triterpenoids unprecedented synthases. Furthermore, addition onoceroids, previously unreported sesquiterpene hydroquinone, biosynthesis involves cyclase, was obtained. Our has broad applicability can serve beneficial platform accessing diverse, unexploited

Язык: Английский

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Global genome mining-driven discovery of an unusual biosynthetic logic for fungal polyketide–terpenoid hybrids

Chemical Science, Год журнала: 2024, Номер 15(8), С. 3011 - 3017

Опубликована: Янв. 1, 2024

Global genome mining resulted in the discovery of an unusual biosynthetic mechanism for fungal meroterpenoids, which dimethylallyltryptophan synthase-type prenyltransferase MfmD installs a farnesyl group subsequent cyclization.

Язык: Английский

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Two Cytochrome P450 Enzymes Form the Tricyclic Nested Skeleton of Meroterpenoids by Sequential Oxidative Reactions

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Апрель 11, 2024

Meroterpenoid clavilactones feature a unique benzo-fused ten-membered carbocyclic ring unit with an α,β-epoxy-γ-lactone moiety, forming intriguing 10/5/3 tricyclic nested skeleton. These compounds are good inhibitors of the tyrosine kinase, attracting lot chemical synthesis studies. However, natural enzymes involved in formation skeleton remain unexplored. Here, we identified gene cluster responsible for biosynthesis clavilactone A basidiomycetous fungus Clitocybe clavipes. We showed that key cytochrome P450 monooxygenase ClaR catalyzes diradical coupling reaction between intramolecular hydroquinone and allyl moieties to form unit, followed by ClaT exquisitely stereoselectively assembles moiety biosynthesis. unprecedentedly acts as macrocyclase catalyze oxidative cyclization isopentenyl nonterpenoid macrocycle, multifunctional ten-electron oxidation accomplish clavilactones. Our findings establish foundation efficient production using synthetic biology approaches provide mechanistic insights into macrocycle fungal meroterpenoids.

Язык: Английский

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Halogenated meroterpenoids with antifungal activities from the Deep-Sea-Derived fungus Acremonium sclerotigenum guided by the genomic and OSMAC strategy

Bioorganic Chemistry, Год журнала: 2025, Номер 156, С. 108186 - 108186

Опубликована: Янв. 19, 2025

Язык: Английский

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Non-Canonical Type II Terpene Cyclases Deliver Rare Terpenoid Architectures

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Март 17, 2025

Terpene cyclases (TCs) catalyze the generation of complex polycyclic terpenoids through elaborate mechanistic cascades. Very little is known about unusual type II TCs responsible for a large diverse family meroterpenoids as indole diterpenoids (IDTs). The radarins are insecticidal and cytotoxic IDTs that possess an core architecture which catalytic machinery unknown. Here, we interrogate genome Aspergillus fresenii to reveal biosynthetic delivering specific radarin scaffold. We demonstrate bespoke regioselective IDT epoxidase (RadM) acts at terminal olefin precursor 3′-geranylgeranylindole, providing access this distinct class architectures. Coexpression with noncanonical TC RadB led biosynthesis C, in skeletal rearrangement proceeds via rare alcoholic deprotonation ketone formation. Our modeling reveals catalysis by enabled unique His residue both proton donor acceptor. Intriguingly, coexpression RadM alternative A. cyclase gene, does not share His, revealed alternate partial cyclization 14,15-epoxy-3′-GGI, producing new decalin IDT. This work solves final piece puzzle full suite architectures, informs engineering efforts, expands repertoire impressive chemistry catalyzed TCs.

Язык: Английский

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Exploiting the Potential of Meroterpenoid Cyclases to Expand the Chemical Space of Fungal Meroterpenoids

Angewandte Chemie International Edition, Год журнала: 2020, Номер 59(52), С. 23772 - 23781

Опубликована: Сен. 18, 2020

Fungal meroterpenoids are a diverse group of hybrid natural products with impressive structural complexity and high potential as drug candidates. In this work, we evaluate the promiscuity early structure diversity-generating step in fungal meroterpenoid biosynthetic pathways: multibond-forming polyene cyclizations catalyzed by yet poorly understood family cyclases. total, 12 unnatural were accessed chemoenzymatically using synthetic substrates. Their complex structures determined 2D NMR studies well crystalline-sponge-based X-ray diffraction analyses. The results obtained revealed degree enzyme experimental which together quantum chemical calculations provided deeper insight into catalytic activity new non-canonical, terpene knowledge paves way to design engineer artificial pathways towards second generation valuable bioactivities based on combinatorial strategies.

Язык: Английский

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