Intramolecular Cyclization and a Retro-Ene Reaction Enable the Rapid Fragmentation of a Vitamin B-Derived Breslow Intermediate.

In solution, analogues of the Breslow intermediate formed during catalysis by benzoylformate decarboxylase (BFDC) undergo rapid, irreversible fragmentation. The ability of BFDC to prevent this reaction and preserve its cofactor is a striking example of an enzyme 'steering' a reactive intermediate towards a productive pathway. To understand how BFDC suppresses the off-pathway reactivity of this Breslow intermediate, a clear mechanistic understanding of the fragmentation reaction is required.

Discovery of a Tambjamine Gene Cluster in Suggests Convergent Evolution in Bipyrrole Natural Product Biosynthesis.

While bacterial natural products are a valuable source of therapeutics, the molecules produced by most biosynthetic gene clusters remain unknown. Tambjamine YP1, produced by , is partially derived from fatty acids siphoned from primary metabolism. A structurally similar tambjamine produced by , BE-18591, had not been linked to a gene cluster.

Sulfite-Catalyzed Nucleophilic Substitution Reactions with Thiamin and Analogous Pyrimidine Donors Proceed an SAE Mechanism.

When treated with SO, thiamin undergoes a substitution reaction to release a thiazole leaving group and the corresponding sulfonate. Although this reaction could proceed via a simple S2-like mechanism, a multistep addition-elimination (SAE) mechanism involving the addition of SO to C6' of the 4-aminopyrimidine of thiamin has also been proposed. Although this reaction has potential utility in the synthesis of substituted pyrimidines and provides a direct analogue to reactions catalyzed by thiaminases, a detailed mechanistic picture of the SO-catalyzed cleavage of thiamin has remained elusive.

The convergence of bacterial natural products from evolutionarily distinct pathways.

As bacteria readily convert simple starting materials into a diverse array of complex molecules with useful bioactivities, these microorganisms and their biosynthetic machinery represent attractive alternatives to traditional chemical syntheses. While the well-documented divergent evolution of biosynthesis has allowed bacteria to explore wide swaths of natural product chemical space, the convergent evolution of these pathways remains a comparably rare phenomenon. The emergence of similar phenotypes within disparate genetic contexts provides a unique opportunity to probe the limitations of natural selection and the predictability and reproducibility of evolution under different constraints.