Akademik Veri Yönetim Sistemi
HIBIT2024 (17th International HIBIT Conference), İstanbul, Türkiye, 18 - 20 Aralık 2024, ss.119, (Özet Bildiri)
Pichia pastoris has emerged as a powerful host for metabolic engineering, attracting significant interest in the production of pharmaceutical precursor metabolites. Overproduction of Tyrosine, a vital amino acid serving as a main precursor to a diversity of pharmaceuticals synthesized through the phenylpropanoid pathway, is highly desired in pharmaceutical applications. To obtain optimal tyrosine overproduction, a logically tailored selection of base metabolic routes utilizing various models is necessary because Pichia pastoris lacks the complete phenylpropanoid pathway and the quality of the metabolic models currently available is unknown. This work examined and compared many Pichia pastoris genome-scale metabolic models (GSMMs). This study examines diÉerent genome-scale metabolic models (GSMMs) of Pichia pastoris to attain maximal tyrosine overproduction. We use MATLAB's "COBRA-Toolbox" to perform constraint-based modeling and examine the benefits and drawbacks of several GSMMs. Particular attention was given to how precisely the models represent tyrosine biosynthesis pathways. The models' capabilities to boost tyrosine production through metabolic flux redistribution, pathway improvements, and targeted genetic modifications were evaluated. Moreover, the models' capacity to adapt to increased tyrosine rates while minimizing the generation of byproducts was investigated in an attempt to provide recommendations for potential approaches to production scaling up in manufacturing environments. The comparative analysis identified the model that enables tyrosine overproduction in Pichia pastoris with minimal knockouts or genetic insertions, oÉering predictions and valuable insights on optimizing the phenylpropanoid pathway. These findings have significant implications for the biomanufacturing of pharmaceutical precursor metabolites, facilitating more sustainable and cost-eÉective production methods, and opening avenues for greener approaches inmanufacturing.