Kim Reynolds

Considering Metabolic Context in Enzyme Evolution and Design Enzymes are often treated as isolated molecular entities when measuring their biochemical activity and designing synthetic sequences. Yet inside the cell, enzymes interact through shared metabolite pools, physical binding, and regulatory feedback. This coordination is necessary for responsive, cohesive metabolic behavior. Moreover, these interactions place constraints on enzyme activity, specificity, abundance, and ultimately sequence. Defining these interaction-mediated constraints is important to understand metabolic evolution and to design synthetic systems. For example, the influence of the cellular and environmental milieu becomes evident when a heterologous enzyme from one species fails to function properly upon transfer to a new host. In this review we consider how cell context shapes enzyme evolution, and in turn, how variations in enzyme biochemistry, biophysics, and abundance impact cell fitness.

Excited to share our new review/perspective on how metabolic (and cellular) context shapes enzyme evolution.
pubs.acs.org/doi/10.1021/...

12.08.2025 13:31 — 👍 1    🔁 1    💬 0    📌 0

After 17 years at UT Southwestern (first as a postdoc, and then starting my lab), I'm excited to be starting a new chapter in The Jenkins Department of Biophysics, at Johns Hopkins University

UTSW friends and colleagues, I will miss you very much!

09.07.2025 21:16 — 👍 5    🔁 1    💬 3    📌 0

New preprint! We carried out the largest complementation and inhibition study for diverse homologs in a single protein family (DHFR) to date. Highlights thread follows... 1/n 🧵

28.01.2025 01:27 — 👍 8    🔁 11    💬 1    📌 0

Combining experiment and computation to tackle scientific problems in the microbial world? Consider applying for our tenure track faculty search in microbial systems biology. Application deadline coming up, Nov 29.

14.11.2024 18:08 — 👍 1    🔁 1    💬 1    📌 0

Announcing a new tenure-track faculty search in microbial systems biology! Come join a fantastic ecosystem of systems biologists and informaticians. Application deadline is Nov 29. To apply: apply.interfolio.com/154339

01.10.2024 03:17 — 👍 4    🔁 11    💬 0    📌 2

Cross section of an enzyme, color coded by mutational epistasis.

Physical protein interactions constrain interface sequence. But what about non-binding "biochemical" interactions in metabolism? We used deep mutational scanning to map sequence constraints for two enzymes that catalyze consecutive metabolic reactions: rdcu.be/dE7xl

19.04.2024 20:24 — 👍 1    🔁 0    💬 0    📌 0

Our new work on (1) mapping genetic interactions in E. coli with titratable CRISPRi and then (2) using these data to build predictive gene expression -> growth rate models is out now in Cell Systems! doi.org/10.1016/j.ce...

09.02.2024 16:36 — 👍 3    🔁 0    💬 0    📌 0

Come join us! We're looking for not just one, but two postdoctoral fellows. We have one position open in biosynth pathway optimization, and another to examine how E. coli responds to perturbations in essential gene abundance. For details: www.utsouthwestern.edu/research/pos...

02.10.2023 19:47 — 👍 5    🔁 2    💬 0    📌 0

We're hiring a new faculty member in Clinical Informatics! Read more and apply at the link.

cu.taleo.net/careersectio...

19.09.2023 19:38 — 👍 9    🔁 25    💬 1    📌 0