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.
Highlights
Microorganisms have gained significant attention as cell factories for the sustainable production of fuels and chemicals, providing great opportunities for a bio-based economy in the post-petroleum era
A recombinant diploid QL60 strain of S. cerevisiae produced 12.5 g/L of ρ-coumaric acid with a productivity of 0.13 g/L/h and a yield of 0.14 g/g sugar under glucoselimited fed-batch fermentation conditions (Liu et al, 2019). This demonstrated superior performance of S. cerevisiae in the production of ρ-coumaric acid over an E. coli strain, in which 168–974 mg/L was produced during flask culture (Kang et al, 2012; Morelli et al, 2017). This remarkable performance of ρ-coumaric acid biosynthesis in S. cerevisiae was achieved by intensive engineering; systematic engineering of the aromatic amino acid (AAA) pathway through debottlenecking a shikimate pathway, enhancing cytochrome P450 activity by overexpression of AtCYB5 and AtATR2; and diverting carbon flux from glycolysis to erythrose 4-phosphate (E4P) by introducing a heterologous phosphoketolase (PHK)-based pathway
As fatty alcohols and fatty esters have been frequently discussed in previous reviews (Hu et al, 2019; Munkajohnpong et al, 2020), we focused on medium-chain and odd-chain fatty acids for which yeast engineering efforts have made noticeable progress in recent years, due to their importance as platform chemicals for the replacement of petroleum in the chemical industry
Summary
Microorganisms have gained significant attention as cell factories for the sustainable production of fuels and chemicals, providing great opportunities for a bio-based economy in the post-petroleum era. This demonstrated superior performance of S. cerevisiae in the production of ρ-coumaric acid over an E. coli strain, in which 168–974 mg/L was produced during flask culture (Kang et al, 2012; Morelli et al, 2017) This remarkable performance of ρ-coumaric acid biosynthesis in S. cerevisiae was achieved by intensive engineering; systematic engineering of the AAA pathway through debottlenecking a shikimate pathway, enhancing cytochrome P450 activity by overexpression of AtCYB5 and AtATR2; and diverting carbon flux from glycolysis to erythrose 4-phosphate (E4P) by introducing a heterologous phosphoketolase (PHK)-based pathway. Palmer et al (2020) demonstrated de novo production of naringenin from Y. lipolytica, with the highest titer among those using S. cerevisiae and E. coli In this study, they introduced the tyrosine-based ρ-coumaroyl-CoA- naringenin pathway and enhanced the metabolic flux from acetyl-CoA to malonyl-CoA through the overexpression of ACC1 and PEX10 (Figure 3B).
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