Current Challenges and Opportunities in Non-native Chemical Production by Engineered Yeasts

Abstract

Yeasts are promising industrial hosts for sustainable production of fuels and chemicals. Apart from efficient bioethanol production, yeasts have recently demonstrated their potential for biodiesel production from renewable resources. The fuel-oriented product profiles of yeasts are now expanding to include non-native chemicals with the advances in synthetic biology. In this review, current challenges and opportunities in yeast engineering for sustainable production of non-native chemicals will be discussed, with a focus on the comparative evaluation of a bioethanol-producing Saccharomyces cerevisiae strain and a biodiesel-producing Yarrowia lipolytica strain. Synthetic pathways diverging from the distinctive cellular metabolism of these yeasts guide future directions for product-specific engineering strategies for the sustainable production of non-native chemicals on an industrial scale.

Survey of nonconventional yeasts for lipid and hydrocarbon biotechnology

“…Yeast and bacteria are generally viewed as favorable industrial organisms because of their fast growth, ease of process scale-up, and lack of dependence on climate and soil quality (Ageitos et al, 2011 ; Thorwall et al, 2020 ). Yeasts are often viewed as preferable to bacteria because of their resistance to phage infection, large repertoire of valuable metabolites, and, in some contexts, their improved tolerance of industrial conditions (Kim et al, 2020 ). There has been interest in using yeasts for the valorization of wastes for both environmental and economic benefits, with lipids and lipid-like molecules serving as an important group of feedstocks and products in this space.…”

Yeast: A platform for the production of L‐tyrosine derivatives

“…Resveratrol, the most investigated chemical of stilbenes (C6‐C2‐C6), is mainly produced by grapevine in nature (Ahmad et al, 2017; Kim et al, 2020). To synthesize resveratrol, one molecular p ‐coumaryl‐CoA and three molecular malonyl‐CoA are required.…”

“…Furthermore, chemical synthesis may not only cause high energy consumption but also results in different toxic intermediates (Mujumdar et al, 2019). During the last two decades, synthetic microbial production has presented shorter process cycles, higher efficiency, and simpler extraction processes to environmentally friendly produce valuable chemicals (Kim et al, 2020). Among microorganisms, yeasts have a thousand years’ history for being domesticated to produce bread and wine, and they are also the preferred cell factory due to the robustness, stability, and easy to culture and genetically manipulated characteristics (Nielsen, 2019).…”

Tips, Tricks, and Potential Pitfalls of CRISPR Genome Editing in Saccharomyces cerevisiae

“…Hence, the development of CRISPR/Cas9 allowed for the rapid expansion of genome engineering into basic research ( Giersch and Finnigan, 2017 ; Thompson et al, 2021 ) as well as industrial biotechnology and synthetic biology ( Stovicek et al, 2015 ; Raschmanová et al, 2018 ; Mitsui et al, 2019 ; Zhang S. et al, 2020 ; Ding et al, 2020 ; Malcı et al, 2020 ; Meng et al, 2020 ; Molina-Espeja, 2020 ; Parapouli et al, 2020 ; Rainha et al, 2020 ; Patra et al, 2021 ). Some important applications of CRISPR/Cas9 genome editing applications in S. cerevisiae involve the production of biopharmaceuticals, biocatalysts, food additives, chemicals, and biofuels ( Hong and Nielsen, 2012 ; Mattanovich et al, 2014 ; Auxillos et al, 2019 ; Mitsui et al, 2019 ; Kim et al, 2020 ; Lacerda et al, 2020 ; Molina-Espeja, 2020 ; Parapouli et al, 2020 ; Utomo et al, 2021 ). Moreover, the expanding CRISPR/Cas toolkit, which includes base editing ( Eid et al, 2018 ; Rees and Liu, 2018 ; Yang et al, 2019 ; Anzalone et al, 2020 ), gene repression and activation ( Gilbert et al, 2013 ; Qi et al, 2013 ; Didovyk et al, 2016 ; Dominguez et al, 2016 ; Brezgin et al, 2019 ; Pickar-Oliver and Gersbach, 2019 ; Xu and Qi, 2019 ; Shakirova et al, 2020 ) as well as alternative Cas proteins and Cas9 variants ( Bao et al, 2015 ; Nakade et al, 2017 ; Yan et al, 2019 ; Paul and Montoya, 2020 ; Thompson et al, 2021 ) have begun to greatly expand what can be accomplished with CRISPR/Cas systems in eukaryotic fungi.…”