Department of Biotechnology
inStem (Institute for Stem Cell Science and Regenerative Medicine)

An economic demand-based framework for prioritization strategies in response to transient amino acid limitations.

Publication Type

Journal Article

Date of Publication

August 23, 2024

Journal

Nature communications

Volume/Issue

15/1

ISSN

2041-1723

Cells contain disparate amounts of distinct amino acids, each of which has different metabolic and chemical origins, but the supply cost vs demand requirements of each is unclear. Here, using yeast we quantify the restoration-responses after disrupting amino acid supply, and uncover a hierarchically prioritized restoration strategy for distinct amino acids. We comprehensively calculate individual amino acid biosynthetic supply costs, quantify total demand for an amino acid, and estimate cumulative supply/demand requirements for each amino acid. Through this, we discover that the restoration priority is driven by the gross demand for an amino acid, which is itself coupled to low supply costs for that amino acid. Demand from metabolic requirements dominate the demand-pulls for an amino acid, as exemplified by the largest restoration response upon disrupting arginine supply. Collectively, this demand-driven framework that drives the amino acid economy can identify novel amino acid responses, and help design metabolic engineering applications.

Alternate Journal

Nat Commun

PubMed ID

39179593

PubMed Central ID

PMC11344141

Authors

Ritu Gupta
Swagata Adhikary
Nidhi Dalpatraj
Sunil Laxman

Keywords

Saccharomyces cerevisiae
Amino Acids
Arginine
Metabolic Engineering