We report a chemo-biocatalytic cascade for the synthesis
of substituted
pyrroles, driven by the action of an irreversible, thermostable, pyridoxal
5′-phosphate (PLP)-dependent, C–C bond-forming biocatalyst
(ThAOS). TheThAOS catalyzes the
Claisen-like condensation between various amino acids and acyl-CoA
substrates to generate a range of α-aminoketones. These products
are reacted with β-keto esters in an irreversible Knorr pyrrole
reaction. The determination of the 1.6 Å resolution crystal structure
of the PLP-bound form ofThAOS lays the foundation
for future engineering and directed evolution. This report establishes
the AOS family as useful and versatile C–C bond-forming biocatalysts.