Biotechnology Advances 47 (2021) 107697 Available online 26 January 2021 0734-9750/© 2021 Elsevier Inc. All rights reserved. Research review paper Metabolic engineering of Saccharomyces cerevisiae for the production of top value chemicals from biorefnery carbohydrates Sara L. Baptista 1 , Carlos E. Costa 1 , Joana T. Cunha, Pedro O. Soares, Lucília Domingues * CEB – Centre of Biological Engineering, University of Minho, Campus Gualtar, Braga, Portugal A R T I C L E INFO Keywords: Saccharomyces cerevisiae Metabolic engineering High-value biobased products Biorefneries Renewable carbon sources ABSTRACT The implementation of biorefneries for a cost-effective and sustainable production of energy and chemicals from renewable carbon sources plays a fundamental role in the transition to a circular economy. The US Department of Energy identifed a group of key target compounds that can be produced from biorefnery carbohydrates. In 2010, this list was revised and included organic acids (lactic, succinic, levulinic and 3-hydroxypropionic acids), sugar alcohols (xylitol and sorbitol), furans and derivatives (hydroxymethylfurfural, furfural and fur- andicarboxylic acid), biohydrocarbons (isoprene), and glycerol and its derivatives. The use of substrates like lignocellulosic biomass that impose harsh culture conditions drives the quest for the selection of suitable robust microorganisms. The yeast Saccharomyces cerevisiae, widely utilized in industrial processes, has been extensively engineered to produce high-value chemicals. For its robustness, ease of handling, genetic toolbox and ftness in an industrial context, S. cerevisiae is an ideal platform for the founding of sustainable bioprocesses. Taking these into account, this review focuses on metabolic engineering strategies that have been applied to S. cerevisiae for converting renewable resources into the previously identifed chemical targets. The heterogeneity of each chemical and its manufacturing process leads to inevitable differences between the development stages of each process. Currently, 8 of 11 of these top value chemicals have been already reported to be produced by recom- binant S. cerevisiae. While some of them are still in an early proof-of-concept stage, others, like xylitol or lactic acid, are already being produced from lignocellulosic biomass. Furthermore, the constant advances in genome- editing tools, e.g. CRISPR/Cas9, coupled with the application of innovative process concepts such as consolidated bioprocessing, will contribute for the establishment of S. cerevisiae-based biorefneries. 1. Introduction In a broad sense, biorefning is described as the sustainable pro- cessing of biomass into a range of marketable biobased products and bioenergy (IEA Bioenergy, 2008). The biorefnery concept comprehends the use of a spectrum of technologies to convert renewable resources, such as lignocellulosic biomass, crude glycerol or cheese whey, into the respective building blocks that can be used for the production of bio- fuels, chemicals or other value-added compounds (Cherubini, 2010). Contrary to the petroleum-based refnery, where natural resources are largely exploited with tremendous waste production, biorefnery em- bodies a major shift by integrating systems that enable full resource usage (Cherubini, 2010). The establishment of a biorefnery fulfls two main purposes: an energy goal, which is driven by the need of renewable energy sources; and an economic goal, focusing on the development of a biobased industry capable of generating proft (Bozell and Petersen, 2010). Considering this, Bozell and Petersen (2010) presented a revised list of biobased product opportunities from renewable carbohydrates, based on the one published in 2004 by the US Department of Energy (Werpy and Petersen, 2004). Based on technological advances, the new top chemical opportunities comprise ethanol, organic acids (lactic, succinic, levulinic and 3-hydroxypropionic acids), sugar alcohols (xylitol and sorbitol), furans (hydroxymethylfurfural, furfural and fur- andicarboxylic acid), biohydrocarbons (isoprene), glycerol and its de- rivatives (Bozell and Petersen, 2010). These top value biobased chemicals were selected following specifc criteria such as knowledge on conversion technology, economic value, industrial viability, size of markets and the ability of a compound to serve as a platform for the production of derivatives. These compounds have been recently the focus of a review that highlighted the recent techniques developed for * Corresponding author. E-mail address: luciliad@deb.uminho.pt (L. Domingues). 1 + These authors contributed equally to this work. Contents lists available at ScienceDirect Biotechnology Advances journal homepage: www.elsevier.com/locate/biotechadv https://doi.org/10.1016/j.biotechadv.2021.107697 Received 9 August 2020; Received in revised form 11 January 2021; Accepted 13 January 2021