Structural highlights
Publication Abstract from PubMed
The C-H bond functionalization has been widely used in chemical synthesis over the past decade. However, regio- and stereoselectivity still remain a significant challenge, especially for inert aliphatic C-H bonds. Here we report the mechanism of three Fe(II)/alpha-ketoglutarate-dependent dioxygenases in bicyclomycin synthesis, which depicts the natural tactic to sequentially hydroxylate specific C-H bonds of similar substrates (cyclodipeptides). Molecular basis by crystallographic studies, computational simulations, and site-directed mutagenesis reveals the exquisite arrangement of three enzymes using mutually orthogonal strategies to realize three different regio-selectivities. Moreover, this programmable selective hydroxylation can be extended to other cyclodipeptides. This evidence not only provides a naturally occurring showcase corresponding to the widely used methods in chemical catalysis but also expands the toolbox of biocatalysts to address the regioselective functionalization of C-H bonds.
Three distinct strategies lead to programmable aliphatic C-H oxidation in bicyclomycin biosynthesis.,Wu L, He JB, Wei W, Pan HX, Wang X, Yang S, Liang Y, Tang GL, Zhou J Nat Commun. 2025 May 19;16(1):4651. doi: 10.1038/s41467-025-58997-8. PMID:40389404[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wu L, He JB, Wei W, Pan HX, Wang X, Yang S, Liang Y, Tang GL, Zhou J. Three distinct strategies lead to programmable aliphatic C-H oxidation in bicyclomycin biosynthesis. Nat Commun. 2025 May 19;16(1):4651. PMID:40389404 doi:10.1038/s41467-025-58997-8
