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Table 2 Metabolic engineering approaches to improve isobutanol production by the yeast S. cerevisiae

From: Biobutanol from cheese whey

Yeast S. cerevisiae engineering technique and carbon source Isobutanol concentration and/or yield Observations Reference
Overexpression of biosynthetic genes ILV2, ILV3, and ILV5 in valine metabolism. Aerobic batch cultures in 40 g/L glucose. 4.12 mg/g glucose First report of isobutanol production by yeast. (2011) [37]
Expression of a cytosolic pathway consisting of ILV2, ILV5, ILV3, ARO10, and ADH2, and deletion of the first gene of the mitochondrial pathway. Batch cultures in 4% glucose. 630 mg/L, The highest titer reported up to the date (2012) [36]
15 mg/g glucose
Characterization of an alternative metabolic pathway for butanol and isobutanol production, using glycine as a substrate via glyoxylate and α -ketoacids intermediates. 58 mg/L Isobutanol from glycine (2013) [38]
Elimination of competing pathways in strains lacking genes encoding members of the pyruvate dehydrogenase complex (LPD1) and resolving the cofactor imbalance by overexpression of enzymes responsible for transhydrogenase-like shunts transforming NADH into NADPH. 24 hours batch fermentation in 100 g/L glucose. 1620 mg/L, The highest titer reported hitherto (2013) [39]
16 mg/g glucose
Compartmentalization of the Ehrlich pathway into mitochondria. 635 mg/L Increased isobutanol production by 260% (2013) [40]
Batch semi-aerobic cultures in 20% glucose.
Fermentation of D-xylose directly to isobutanol: Overexpression of an optimized, cytosolically localized valine biosynthesis pathway together with xylose isomerase XylA from Clostridium phytofermentans, transaldolase Tal1 and xylulokinase Xks1, ketoacid decarboxylase Aro10 and alcohol dehydrogenase Adh2. 1.36 mg/L Isobutanol from xylose (2013) [41]
0.16 mg/g D-xylose.
Genes involved in isobutanol production (ILV2, ILV3, ILV5, ARO10, and ADH2) overexpressed in an ald6Δbat1Δ strain (to eliminate competing pathways) expressing LEU3Δ601 (to activate transcription of endogenous genes in the valine and leucine biosynthetic pathways) 376.9 mg /L Transcriptional activation (2014) [42]
Closed tube cultures with 100 g/L of glucose as substrate