Fenestranes, a specific class of natural products, contain four fused rings that share a central quaternary carbon atom. The fungal natural product penifulvin A (1) is a potent insecticidal sesquiterpene that features the [5.5.5.6]dioxafenestrane ring. Although the chemical synthesis of 1 has been achieved recently, the enzymes catalysing the cyclization and oxidation of FPP to 1 remain unknown. In this work, we identified a concise pathway that uses only three enzymes to produce 1. A new sesquiterpene cyclase (PeniA) generates the angular triquinane scaffold silphinene (6). A cytochrome P450 (PeniB) and a flavin‐dependent monooxygenase (PeniC) catalyse a series of oxidation reactions to transform 6 into 1, including oxidation of the C15 methyl group to a carboxylate moiety, oxidative coupling of the C15 carboxylate and the C1‐C2 olefin to form a γ‐lactone, and Baeyer–Villiger oxidation to form a δ‐lactone. Our results demonstrate the highly concise and efficient ways in which fungal biosynthetic pathways can generate complex sesquiterpene scaffolds.

Divergent biosynthesis is widely employed in nature to promote chemical diversity, usually depending on multifunctional enzymes from different environments, for the generation of diverse biologically active compounds. In this work, we identified two parallel and complex pathways (peni and aspe) of fungal dioxafenestrane sesquiterpenes from terrestrial fungus and marine-derived fungus, respectively. These two pathways share a common intermediate but are different in late-stage tailoring steps such as Baeyer–Villiger oxidation in δ-lactone formation and hydroxylation carried on nonactivated carbons. It is important that a distinctive Baeyer–Villiger monooxygenase (BVMO) AspeB from a marine-derived fungus source and a large number of substrate-tolerant α-ketoglutarate-dependent dioxygenases (α-KGDs, AspeC/D, and PeniD/F) and their artificial mutants used for structural diversity are discovered. Moreover, an acetylation step catalyzed by the acetyltransferase PeniE in the peni pathway was also identified. Our work not only reveals a representative example of the evolutionary relationship between natural product generation and corresponding metabolic enzymes from different environments but also provides valuable biocatalysts for nonactivated carbon oxidation modification.

Fenestranes,aspecific class of natural products, contain four fused rings that share acentral quaternary carbon atom. The fungal natural product penifulvin A( 1)i sapotent insecticidal sesquiterpene that features the [5.5.5.6]dioxafenestrane ring. Although the chemical synthesis of 1 has been achieved recently,t he enzymes catalysing the cyclization and oxidation of FPP to 1 remain unknown. In this work, we identified ac oncise pathway that uses only three enzymes to produce 1.Anew sesquiterpene cyclase (PeniA) generates the angular triquinane scaffold silphinene (6). Acytochrome P450 (PeniB) and af lavin-dependent monooxygenase (PeniC) catalyse as eries of oxidation reactions to transform 6 into 1, including oxidation of the C15 methyl group to ac arboxylate moiety,oxidative coupling of the C15 carboxylate and the C1-C2 olefin to form a g-lactone,and Baeyer-Villiger oxidation to form a d-lactone.O ur results demonstrate the highly concise and efficient ways in which fungal biosynthetic pathways can generate complex sesquiterpene scaffolds.

In this study, we prepared three different silicon quantum dots (SiQDs-1, SiQDs-2 and SiQDs-3) by hydrothermal synthesis with rose Bengal as the reducing agent and triacetoxy(methyl)silane and allyloxytrimethylsilane as silicon sources.