Abstract
The beta-hydroxy acid 3-hydroxypropionic acid (3-HP) is an attractive platform compound that can be used as a precursor for many commercially interesting compounds. In order to reduce the dependence on petroleum and follow sustainable development, 3-HP has been produced biologically from glucose or glycerol. It is reported that 3-HP synthesis pathways can be constructed in microbes such as Escherichia coli, Klebsiella pneumoniae and the yeast Saccharomyces cerevisiae. Among these host strains, yeast is prominent because of its strong acid tolerance which can simplify the fermentation process. Currently, the malonyl-CoA reductase pathway and the β-alanine pathway have been successfully constructed in yeast. This review presents the current developments in 3-HP production using yeast as an industrial host. By combining genome-scale engineering tools, malonyl-CoA biosensors and optimization of downstream fermentation, the production of 3-HP in yeast has the potential to reach or even exceed the yield of chemical production in the future.
Highlights
With the reduction of obtainable fossil fuels and sustainable development becoming the mainstream of the world, petroleum-based compounds are gradually being replaced by bio-based compounds to meet the increasing demands for bulk materials and fine chemicals alike (Nielsen and Keasling, 2016; Chen et al, 2018a)
Biosynthesis methods have many advantages, including cheaper substrates, mild reaction conditions and simple operation, which are compatible with sustainable development, and the reduced amounts of byproducts help reduce the cost of production
Improving the Supply of the Precursor Acetyl-CoA Malonyl-CoA is an important substrate for the production of 3-hydroxypropionic acid (3-HP) by malonyl-CoA reductase (MCR)
Summary
With the reduction of obtainable fossil fuels and sustainable development becoming the mainstream of the world, petroleum-based compounds are gradually being replaced by bio-based compounds to meet the increasing demands for bulk materials and fine chemicals alike (Nielsen and Keasling, 2016; Chen et al, 2018a). Engineering Yeast for 3-HP Production that 3-HP has a wide market and great application value It can be obtained by chemical synthesis and biosynthesis methods. Improving the Supply of the Precursor Acetyl-CoA Malonyl-CoA is an important substrate for the production of 3-HP by MCR It is mainly produced from acetyl-CoA by ACC1, and known as a flux-controlling step (Tehlivets et al, 2007; Chen et al, 2018b). When the endogenous ADH2 (alcohol dehydrogenase) was co-expressed with ALD6 (NADP-dependent aldehyde dehydrogenase), ACC1 and a codon optimized ACS variant, ACSse (an acetylation-insensitive acetyl-CoA synthetase from Salmonella enterica), the flux was successfully redirected from ethanol to acetyl-CoA in the cytosol, which improved 3-HP production to 210 mg/L, up to twofold of the control strain (Chen et al, 2014).
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