Innovative Tools and Strategies for Optimizing Yeast Cell Factories

• Published in: Trends in biotechnology (Regular ed.) 2021-05, Vol.39 (5), p.488-504
• Main Authors: Guirimand, Gregory, Kulagina, Natalja, Papon, Nicolas, Hasunuma, Tomohisa, Courdavault, Vincent
• Format: Article
• Language: English
• Subjects: adaptive laboratory evolution; Biosynthesis; cis/trans regulators; Cloning; Combinatorial analysis; CRISPR; Cutting tools; Deoxyribonucleic acid; DNA; Dynamic control; Efficiency; Factories; Fluxes; Gene expression; Genetic engineering; Genome editing; Genomes; Industrial engineering; Life Sciences; Mammals; Manufacturing engineering; Metabolic engineering; metabolic fluxes; Metabolic pathways; Metabolism; Microbiology and Parasitology; Microorganisms; Mycology; Narcotics; Optimization; Plasmids; Post-transcription; Reconfiguration; Regulators; subcellular compartmentation; Yeast; Yeasts
• ISSN: 0167-7799; 1879-3096
• DOI: 10.1016/j.tibtech.2020.08.010

Metabolic engineering (ME) aims to develop efficient microbial cell factories that can produce a wide variety of valuable compounds, ideally at the highest yield and from various feedstocks. We summarize recent developments in ME methods for tailoring different yeast cell factories (YCFs). In particular, we highlight the most timely and cutting-edge molecular tools and strategies for biosynthetic pathway optimization (including genome-editing tools), combinatorial transcriptional and post-transcriptional engineering (cis/trans regulators), dynamic control of metabolic fluxes (e.g., rewiring of primary metabolism), and spatial reconfiguration of metabolic pathways. Finally, we discuss challenges and perspectives for adaptive laboratory evolution (ALE) of yeast to advance ME of microbial cell factories. Bioproduction of many medicinal natural products that are not readily available is the best option to ensure a stable supply of pharmaceuticals.Among the many bioproduction host microorganisms, yeasts (including Saccharomyces cerevisiae and other, nonconventional strains) constitute valuable platforms for industrial bioproduction of natural products.Progress in metabolic engineering and synthetic biology has enabled the development of yeast cell factories (YCFs) that are capable of efficiently producing natural products.Implementation of YCFs relies on molecular tools and strategies for the optimization of biosynthetic pathways, dynamic control, and spatial (re)configuration of metabolic fluxes in vivo.Several of these tools and strategies still have limitations, but constant effort in the field is dedicated to overcoming them to optimize YCFs.