Allwin McDonald

Assistant Professor

Offices, Departments, or Centers: Chemistry ,

My research focuses on biocatalytic syntheses of medicinal compounds. Enzymatic syntheses provide high specificity under biologically friendly conditions. This high specificity means that enzymes are naturally well-suited for cascade syntheses. I am interested in developing enzymatic cascades that provide advantages over traditional synthetic methodologies.

Additionally, by leveraging the biocatalysis factories that are living cells, engineered cascades can function in vivo. This allows syntheses to take place in bacteria, yeast, or plants, further expanding useful cascade targets. These engineered pathways will improve yield and accessibility of currently tricky-to-synthesize compounds.

Additionally, I am working on designing high-throughput screening methods. Too often, high-throughput screens are limited to a small-subset of enzymatic reactions (a notable example here being hydrolases) or involve interactions with transcription factors/DNA. By taking advantage of unique ways small molecules interact with cellular metabolism, I seek to develop more general in vivo screens of biocatalysts involved in specialized metabolism.

Education and Degrees

B.A. Ripon College – 2017

Ph.D. University of Wisconsin-Madison – 2022

Postdoctoral Scientist with Sarah O’Connor at the Max Planck of Chemical Ecology – 2022-2025

Selected Publications

Carr S.C.*; McDonald A.D.*; Langley C.*; Grabe V.; Gase K.; O’Connor S.E. “Protein-Protein Interactions Modulate a Key Branchpoint in Monoterpene Indole Alkaloid Biosynthesis.” 2026, 21, 8-13.

McDonald, A.D.; Nakamura, Y.; Schotte, C.; Titchiner, G.; Lau, K,; Alam, R.; Lopes, A.A.; Buell, C.R.; O’Connor. S.E. “Enzymatic epimerization of monoterpene indole alkaloids in Kratom.” Nature Chemical Biology., 2025.

McDonald, A.D.*; Ellis, J. M.*; Steger-Wilson, L.; Campbell, M.; Buller, A.R. “Active site diversification of a non-canonical amino acid decarboxylase by merging substrate multiplexed screening with computationally guided recombination.” Protein Science 2025, 34 (11), e70356.

McDonald, A.D.; Bruffy, S.K.; Kasat, A.T.; Buller, A.R. “Engineering a promiscuous C-C bond forming cascade for the synthesis of chiral 1,2-amino alcohols.” Angewandte Chemie, 2022, 61, No. e202212637.

McDonald, A.D.*; Higgins, P.M.*; Buller, A.R. “Substrate multiplexed protein engineering facilitates promiscuous biocatalytic synthesis.” Nat. Comm., 2022, 13, 5242.

Thompson, C.M.; McDonald, A.D.; Yang, H.; Cavagnero, S.; Buller, A.R. “Modular control of L-tryptophan isotopic substitution via an efficient biosynthetic cascade.” Org. Biomol. Chem. 2020. 18, 4189–4192.

McDonald, A.D.; Perkins, L.J.; Buller, A.R. “Facile in vitro biocatalytic production of diverse tryptamines.” ChemBioChem. 2019. 20, 1939–1944.