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Biosynthesis

A carbonate architect emerges

Nature Chemical Biology volume 10, pages 486–487 (2014)Cite this article

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Carbonates are known to exist in natural products, but their biosynthesis has not been linked to any enzymes. An unusual fungal Baeyer-Villiger monooxygenase CcsB is now revealed to catalyze an in-line carbonate formation via a two-step mechanism of oxygen atom insertions.

The biosynthesis of complex polyketide and nonribosomal peptide natural products routinely involves formation of a core structure by stepwise chain elongation followed by enzymatic tailoring steps such as acylation, methylation, glycosylation and redox transformation. Among the fascinating enzymes that catalyze these tailoring reactions are flavin-dependent monooxygenases1. These are multifunctional enzymes that catalyze a variety of different types of C-O bond formation, including Baeyer-Villiger (BV) oxidations2,3, catalyzed by the BV monooxygenases (BVMOs). The key intermediate flavin-peroxide species (Fl-4a-OO−) serves as a nucleophilic equivalent in BV transformations in the conversion of keto groups to esters in numerous natural product pathways. In contrast, oxidation to the carbonate moiety has rarely been observed in either chemical synthesis or enzymatic transformation, and its biosynthetic origins are unknown. Hu et al.4 now demonstrate one route by which a carbonate moiety is generated in their biochemical characterization of a remarkable multifunctional BVMO enzyme, CcsB, in the biosynthetic pathway to the polyketide-peptide cytochalasin E in the fungus Aspergillus clavatus.

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Figure 1: The mechanism of carbonate formation catalyzed by CcsB.

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  1. Yuhui Sun is in the Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) at the School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.,

    Yuhui Sun

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Correspondence to Yuhui Sun.

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Sun, Y. A carbonate architect emerges. Nat Chem Biol 10, 486–487 (2014). https://doi.org/10.1038/nchembio.1531

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