In the current research paper, the following process-design problem is considered: can the activity, thermostability and simplified thioester data obtained for the designed V79 variants of the engineered Thermus thermophilus \(\alpha\)-oxoamine synthase be converted into a repeatable selection process for the catalysts used in aminoketone and pyrrole synthesis? To address this challenge, thermokinetic substrate-lattice prioritization, a route-selection procedure, which distinguishes between discovery potential and preparative capacity, is developed. Unlike a routine set of enzymatic screening assays, the current data set represents the V79 variant matrix characterized by amino acid acceptance, acyl-CoA donor range, residual activity after 70 and 90 \(^\circ\)C thermal stress, acetyl-SNAc resistance and the glycine/acetyl-SNAc/methyl acetoacetate pyrrole synthesis pathway. In this approach, the observable activity is presented as a substrate-lattice function and merged with normalized heat stability, acyl donor tolerance and SNAc-based route efficiency metrics. The resulting selection process produces a non-redundant ranking: V79G variant is recommended for exploration of novel amino acids and hydrophobic acyl donor routes, while V79S should be employed in propargyl and selected aromatic acyl donors route development. Finally, V79A variant is recommended for preparative SNAc-based pyrrole synthesis due to its broad amino acid range, best severe temperature stability among all active engineered mutants and 35% analytical pyrrole yield achieved at 60 \(^\circ\)C.
