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pcSecYeastSpecies: Cross-species proteome-constrained modeling of yeast protein secretion

This repository contains the code and models used in the study:

Cross-species proteome-constrained modeling reveals trade-offs in yeast protein secretion under temperature and glycosylation stress

We built on the pcSecYeast model for Saccharomyces cerevisiae and developed proteome-constrained protein secretion models for Komagataella phaffii and Kluyveromyces marxianus. By integrating genome-scale metabolism, detailed secretory pathway representations, proteome allocation constraints, temperature-dependent enzyme kinetics, and humanized glycosylation modules, this framework enables quantitative, cross-species analysis of secretion capacity, metabolic trade-offs, and stress responses under industrially relevant conditions.


Model Construction

Proteome-constrained secretion models were constructed from a common template model using species-specific build scripts.
Models for S. cerevisiae, K. phaffii, and K. marxianus are generated using buildModel_pcSecYeast.m, buildModel_pcSecPichia.m, and buildModel_pcSecKmarx.m, respectively.


Simulation and Analysis

All simulation scripts required to reproduce the analyses in the manuscript are provided in the corresponding species-specific folders under Code/.
Scripts to reproduce all manuscript figures are located in Code/Figures/; each figure script loads the processed results and generates the corresponding plots.
Simulation outputs are saved in the Results/ directory.


Installation

Required software

Please ensure that all required toolboxes and solvers are properly installed and added to the MATLAB path before running the scripts.

Contact

Lizheng Liu (GitHub: @Zephyr-112), Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China

Feiran Li (GitHub: @feiranl), Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China

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