The accelerating and thorough treatment of chronic wounds still represents a major unmet medical need owing to the complex symptoms resulting from metabolic disorder of the wound microenvironment. Although numerous strategies and bioactive hydrogels are developed, an effective and widely used method of chronic wound treatment remains a bottleneck. With the aim to accelerate chronic wound healing, many hydrogel dressings with antioxidant functions have emerged and are proven to accelerate wound healing, especially for chronic wound repair. The new strategy in chronic wound treatment brought by antioxidant hydrogels is of great significance to human health. Here, the application of antioxidant hydrogels in the repair of chronic wounds is discussed systematically, aiming to provide an important theoretical reference for the further breakthrough of chronic wound healing.

Advances and Impact of Antioxidant Hydrogel in Chronic Wound Healing.

Dimericbiscognienyne A: A Meroterpenoid Dimer from Biscogniauxia sp. with New Skeleton and Its Activity.

Secondary metabolites of higher fungi (mushrooms) are an underexplored resource compared to plant-derived secondary metabolites. An increasing interest in mushroom natural products has been noted in recent years. This chapter gives a comprehensive overview of the secondary metabolites from higher fungi, with 765 references highlighting the isolation, structure elucidation, biological activities, chemical syntheses, and biosynthesis of pigments, nitrogen-containing compounds, and terpenoids from mushrooms. Mushroom toxins are also included in each section.

Secondary Metabolites from Higher Fungi

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

The chemistry and biology of fungal meroterpenoids (2009-2019).

https://pubs.rsc.org/en/content/articlepdf/2021/np/d1np00032b

Genome mining methods to discover bioactive natural products.

The oxidative decarboxylation of prenyl 4-hydroxybenzoate to prenylhydroquinone has been frequently proposed for the biosynthesis of prenylated (hydro)quinone derivates (sometimes meroterpenoids), yet no corresponding genes or enzymes have so far been reported. A FAD-binding monooxygenase (VibMO1) was identified that converts prenyl 4-hydroxybenzoate into prenylhydroquinone and is likely involved in the biosynthesis of vibralactones and other meroterpenoids in the basidiomycete Boreostereum vibrans. Feeding of 3-allyl-4-hydroxybenzylalcohol, an analogue of the vibralactone pathway intermediate 3-prenyl-4-hydroxybenzylalcohol, generated 20 analogues with different scaffolds. This demonstrated divergent pathways to skeletally distinct compounds initiating from a single precursor, thus providing the first insight into a novel biosynthetic pathway for 3-substituted γ-butyrolactones from a shikimate origin.

A Monooxygenase from Boreostereum vibrans Catalyzes Oxidative Decarboxylation in a Divergent Vibralactone Biosynthesis Pathway

Vibralactone is isolated from the basidiomycete fungus Boreostereum vibrans as one of the strongest lipase inhibitors. Its unusual β-lactone-fused bicycle is derived from an aryl ring moiety by an oxidative ring-expansion prior to an intramolecular cyclization. Herein, we report the discovery of the cyclase VibC which belongs to the α/β-hydrolase superfamily and is involved in the vibralactone biosynthesis. Biochemical and crystal studies suggest that VibC may catalyze an aldol or an electrocyclic reaction initiated by the Ser-His-Asp catalytic triad. For the aldol and pericyclic chemistry in living cells, VibC is a unique hydrolase performing the carbocycle formation of an oxepinone to a fused bicyclic β-lactone. This presents a naturally occurring, new enzymatic reaction in both aldol and hydrolase (bio)chemistry that will guide future exploitation of these enzymes in synthetic biology for chemical-diversity expansion of natural products.

A Hydrolase-Catalyzed Cyclization Forms the Fused Bicyclic β-Lactone in Vibralactone

Recombinant polyphenol oxidases for production of theaflavins from tea polyphenols.

Diterpene synthases facilitating production of the kaurane skeleton of eriocalyxin B in the medicinal plant Isodon eriocalyx.

Abstract Oxepinone rings represent one of structurally unusual motifs of natural products and the biosynthesis of oxepinones is not fully understood. 1,5- Seco -vibralactone ( 3 ) features an oxepinone motif and is a stable metabolite isolated from mycelial cultures of the mushroom Boreostereum vibrans . Cyclization of 3 forms vibralactone ( 1 ) whose β-lactone-fused bicyclic core originates from 4-hydroxybenzoate, yet it remains elusive how 4-hydroxybenzoate is converted to 3 especially for the oxepinone ring construction in the biosynthesis of 1 . In this work, using activity-guided fractionation together with proteomic analyses, we identify an NADPH/FAD-dependent monooxygenase VibO as the key enzyme performing a crucial ring-expansive oxygenation on the phenol ring to generate the oxepin-2-one structure of 3 . The crystal structure of VibO reveals that it forms a dimeric phenol hydroxylase-like architecture featured with a unique substrate-binding pocket adjacent to the bound FAD. Computational modeling and solution studies provide insight into the likely VibO active site geometry, and suggest possible involvement of a flavin-C4a-OO(H) intermediate. 

Ke-Na Feng

Papers

A Monooxygenase from Boreostereum vibrans Catalyzes Oxidative Decarboxylation in a Divergent Vibralactone Biosynthesis Pathway

A Hydrolase-Catalyzed Cyclization Forms the Fused Bicyclic β-Lactone in Vibralactone

Recombinant polyphenol oxidases for production of theaflavins from tea polyphenols.

Diterpene synthases facilitating production of the kaurane skeleton of eriocalyxin B in the medicinal plant Isodon eriocalyx.

A flavin-monooxygenase catalyzing oxepinone formation and the complete biosynthesis of vibralactone