Summary
Ancestrally reconstructed enzymes are not always more generalist than extant enzymes. (1) found that an ancestral tryptophan synthase did not have greater substrate breadth than modern enzymes. This contrasts with prior hypotheses that generalist ancestral enzymes evolved specificity over time, which is corroborated by other reports, such as ancestral L-arginine oxidase from (2), and transaminase from (3).
1.
Busch F, Rajendran C, Heyn K, Schlee S, Merkl R, Sterner R. Ancestral Tryptophan Synthase Reveals Functional Sophistication of Primordial Enzyme Complexes. Cell Chemical Biology. 2016;23(6):709–15. Available from: https://doi.org/10.1016/j.chembiol.2016.05.009
2.
Nakano S, Niwa M, Asano Y, Ito S. Following the Evolutionary Track of a Highly Specific l -Arginine Oxidase by Reconstruction and Biochemical Analysis of Ancestral and Native Enzymes. Applied and Environmental Microbiology. 2019;85(12). Available from: https://doi.org/10.1128/aem.00459-19
3.
Wilding M, Peat TS, Kalyaanamoorthy S, Newman J, Scott C, Jermiin LS. Reverse engineering: transaminase biocatalyst development using ancestral sequence reconstruction. Green Chemistry. 2017;19(22):5375–80. Available from: https://doi.org/10.1039/c7gc02343j