Biotechnology and Bioprocess Engineering 2024; 29(1): 35-67  
Reconstruction of genome‑scale metabolic models of non‑conventional yeasts: current state, challenges, and perspectives
Eduardo Luís Menezes de Almeida1 · Eduard J. Kerkhoven2,3 · Wendel Batista da Silveira1
1 Laboratory of Microbial Physiology, Department of Microbiology, Universidade Federal de Viçosa, Viçosa, Minas Gerais 36570‑900, Brazil
2 Systems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden
3 SciLifeLab, Chalmers University of Technology, 412 96 Gothenburg, Sweden
Correspondence to: Wendel Batista da Silveira
wendel.silveira@ufv.br
Received: July 12, 2023; Revised: October 2, 2023; Accepted: October 16, 2023; Published online: February 13, 2024.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Non-conventional yeasts are promising cell factories to produce lipids and oleochemicals, metabolites of industrial interest (e.g., organics acids, esters, and alcohols), and enzymes. They can also use different agro-industrial by-products as substrates within the context of a circular economy. Some of these yeasts can also comprise economic and health burdens as pathogens. Genome-scale metabolic models (GEMs), networks reconstructed based on the genomic and metabolic information of one or more organisms, are great tools to understand metabolic functions and landscapes, as well as propose engineering targets to improve metabolite production or propose novel drug targets. Previous reviews on yeast GEMs have mainly focused on the history and the evaluation of Saccharomyces cerevisiae modeling paradigms or the accessibility and usability of yeast GEMs. However, they did not describe the reconstruction strategies, limitations, validations, challenges, and research gaps of non-conventional yeast GEMs. Herein, we focused on the reconstruction of available non-Saccharomyces GEMs, their validation, underscoring the physiological insights, as well as the identification of both metabolic engineering and drug targets. We also discuss the challenges and knowledge gaps and propose strategies to boost their use and novel reconstructions.
Keywords: Metabolic engineering · Yeast · Metabolic modeling · Non-Saccharomyces


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