Controlling circuitry underlies the growth optimization of Saccharomyces cerevisiae

Nguyen, Viviana; Xue, Pu; Li, Yifei; Zhao, Huimin; Lu, Ting

doi:10.1016/j.ymben.2023.09.013

Controlling circuitry underlies the growth optimization of Saccharomyces cerevisiae

Journal Article · Wed Nov 01 00:00:00 EDT 2023 · Metabolic Engineering

DOI:https://doi.org/10.1016/j.ymben.2023.09.013· OSTI ID:2309749

Nguyen, Viviana ^[1]; Xue, Pu ^[2]; Li, Yifei ^[3]; Zhao, Huimin ^[2]; Lu, Ting ^[4]

Univ. of Illinois at Urbana-Champaign, IL (United States); Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States); University of Illinois Urbana-Champaign
Univ. of Illinois at Urbana-Champaign, IL (United States); Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States)
Univ. of Illinois at Urbana-Champaign, IL (United States). Center for Biophysics and Quantitative Biology; Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States)
Univ. of Illinois at Urbana-Champaign, IL (United States). Center for Biophysics and Quantitative Biology; Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States); Univ. of Illinois at Urbana-Champaign, IL (United States). National Center for Supercomputing Applications

Microbial growth emerges from coordinated synthesis of various cellular components from limited resources. In Saccharomyces cerevisiae, cyclic AMP (cAMP)-mediated signaling is shown to orchestrate cellular metabolism; however, it remains unclear quantitatively how the controlling circuit drives resource partition and subsequently shapes biomass growth. Here we combined experiment with mathematical modeling to dissect the signaling-mediated growth optimization of S. cerevisiae. We showed that, through cAMP-mediated control, the organism achieves maximal or nearly maximal steady-state growth during the utilization of multiple tested substrates as well as under perturbations impairing glucose uptake. However, the optimal cAMP concentration varies across cases, suggesting that different modes of resource allocation are adopted for varied conditions. Under settings with nutrient alterations, S. cerevisiae tunes its cAMP level to dynamically reprogram itself to realize rapid adaptation. Moreover, to achieve growth maximization, cells employ additional regulatory systems such as the GCN2-mediated amino acid control. This study establishes a systematic understanding of global resource allocation in S. cerevisiae, providing insights into quantitative yeast physiology as well as metabolic strain engineering for biotechnological applications.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of Illinois at Urbana-Champaign, IL (United States). Center for Advanced Bioenergy and Bioproducts Innovation (CABBI)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: SC0018420

OSTI ID:: 2309749

Journal Information:: Metabolic Engineering, Journal Name: Metabolic Engineering Vol. 80; ISSN 1096-7176

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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