. Author manuscript; available in PMC: 2021 Dec 1.

Published in final edited form as: Curr Opin Chem Biol. 2020 Oct 5;59:182–192. doi: 10.1016/j.cbpa.2020.08.005

Table 1.

Summary of strategies for non-ethanol chemical production in S. cerevisiae

Reference	Pdc⁻ phenotype	Relieve Crabtree effect through ALE	Alternate acetyl-CoA routes	NAD⁺ regeneration	Metabolic control of ethanol production	Alternate carbon source	Product(s)	Yield (g/g carbon source)	Titer (g/L)	Conditions (carbon source, medium, batch/fed-batch, vessel, conditions)
[71]	✓	✓	✓				Acetate	0.14^a	< 0.5	Glucose, minimal medium, batch, flask, aerobic
[71]	✓	✓	✓				Pyruvate	0.007^a	< 0.5	Glucose, minimal medium, batch, flask, aerobic
[25]	✓	✓		✓			2,3-Butanediol	0.28	96.2	Glucose, YP medium, fed-batch, bioreactor, aerobic
							Glycerol	0.09^a	>30^c
							Acetoin	0.01^a	~5^c
[33]	✓			✓			2,3-Butanediol	0.407	72.91	Glucose, YP medium, fed-batch, flask, aerobic
[33]	✓			✓			Acetoin	0.01^a	1.38	Glucose, YP medium, fed-batch, flask, aerobic
[34]	✓			✓			2,3-Butanediol	0.359	32.31^c	Glucose + ethanol, minimal media, batch, bioreactor, oxygen-limited
							Glycerol	0.069	6.21^c
							Acetoin	0.052	4.68^c
[35]	✓		✓	✓			2,3-Butanediol	0.404	154.3	Glucose, YP medium, fed-batch, bioreactor, full aeration followed by oxygen limitation
							Glycerol	0.088	33.5^c
							Acetate	0.006^a	2.3
[36]	✓	✓	✓	✓			2,3-Butanediol	0.462	108.6	Glucose, YP medium, fed-batch, bioreactor, full aeration followed by oxygen limitation
							Acetoin	0.02^a	4.6
							Acetate	0.0004^a	0.1
[27]	✓	✓		✓			2,3-Butanediol	0.27	81.0	Glucose, synthetic defined medium, fed-batch, flask, mild aerobic
							Glycerol	0.239^a	71.8
							Succinate	0.013^a	4.0
[72]	✓			✓			n-Butanol	0.012	0.130	Glucose + pantothenate, SMD medium, flask, semi-anaerobic
							Ethanol	0.10	~1^c
							Glycerol	0.17	~2^c
[43]	✓	✓		✓			Isobutanol	0.0074^a	^b	Glucose, SMG medium + Tween-80 + ergosterol, batch, serum bottle, microaerobic
							Ethanol	0.033^a	^b
							Glycerol	0.26^a	^b
							Pyruvate	0.02^a	^b
							2,3-butanediol	0.325^a	^b
							Dihydroxyisovalerate	0.05^a	^b
							Isobutyrate	0.03^a	^b
[61]				✓	✓		Isobutanol	0.0535	8.49	Glucose, SC-Ura, fed-batch, bioreactor, microaerobic
							2-Methyl-1-butanol	0.01417	2.38
							Ethanol	0.187	39.8
							Glycerol	^b	^b
[28]	✓	✓	✓	✓			Free fatty acids	0.1	25	Glucose, minimal N₂-limited medium, fed-batch, bioreactor, aerobic
[28]	✓	✓	✓	✓			Glycerol	^b	^b
[42]	✓	✓		✓			Malic acid	0.31^a	59	Glucose, synthetic medium, batch, flask, aerobic
							Succinate	0.04^a	8
							Glycerol	0.13^a	25
							Pyruvate	0.02^a	3
							Fumarate	0.01^a	2
[54]	✓	✓		✓			Succinic acid	0.044^a	2.2	Glucose + formate, mineral salt medium, deep-well plate, microaerobic
							Pyruvate	0.364^a	18.2
							Malate	0.022^a	1.1
							Glycerol	0.076^a	3.8
[60]				✓	✓		Gluconate	^b	2.31	Glucose, synthetic defined, batch, culture tube, semi-anaerobic
							Ethanol	^b	1.01
							Glycerol	^b	^b
[41]	✓			✓			Lactic acid	0.6	80	Glucose, YP medium, fed-batch, bioreactor, aerobic
							Ethanol	0.01	1.6
							Glycerol	0.02	2.6
[40]				✓			Lactic acid	0.8	112.0	Glucose, YP medium, fed-batch, flask, aerobic
[40]				✓			Ethanol	0.02^a	2.6	Glucose, YP medium, fed-batch, flask, aerobic
[69]	✓			✓		✓	Lactic acid	0.43^a	7.8	2-stage sugar consumption (ethanol then xylose), YP medium, batch, bioreactor, aerobic followed by microaerophilic
							Acetate	0.16^a	3^c
							Xylitol	0.01^a	0.17^c
[70]				✓		✓	Lactic acid	0.67	60	Xylose, YP medium, batch, flask, aerobic
							Ethanol	0.01^a	<1
							Xylitol	0.01^a	<1
							Glycerol	0.01^a	<1
							Acetate	0.01^a	<1
[68]	✓		✓	✓		✓	2,3-Butanediol	0.46^a	96.8	Xylose + glucose, YP medium, fed-batch, bioreactor, microaerobic
							Glycerol	0.11^a	23.3
							Ethanol	0.08^a	16.3
							Xylitol	0.03^a	5.9
[73]	✓			✓		✓	2,3-Butanediol	0.26^a	43.6	Xylose + glucose, YP medium, fed-batch, bioreactor, microaerobic
							Glycerol	0.26^a	45
							Xylitol	0.03^a	4.7
[63]				✓		✓	Isobutanol	0.026^a	2.6	Xylose, nutrient-rich Verduyn medium, fed-batch, bioreactor, aerobic
							Ethanol	0.275^a	~27.5^c
							Glycerol	0.10^a	~10 g/L^c
[62]				✓		✓	Isobutanol	0.0196	3.10	Xylose, synthetic medium, fed-batch, conical tube, semi-anaerobic
							2-Methyl-1-butanol	0.0053	0.79
							Ethanol	0.32^a	<50^c
							Glycerol	^b	^b
[67]				✓		✓	1,2-Propanediol	0.129	4.3	Glycerol, YP medium, batch, bioreactor, aerobic
[67]				✓		✓	Ethanol	~0^a	~0^c	Glycerol, YP medium, batch, bioreactor, aerobic

Bold = product of interest

Italics = by-product

Absence of ethanol or glycerol in a row indicates it was not detected or that the yield or titer was <0.01

^{a =}

Yield not directly reported. Yield is either read from a graph, converted from a molar yield, calculated as g/g consumed carbon source, or calculated by dividing production rate by carbon source uptake rate.

^{b =}

Not reported

^{c =}

Titer not directly reported. Titer is either read from a graph, converted from molar concentration, or calculated as g/L fed carbon source, which is quantified by multiplying the reported yield (g/g carbon source) by the carbon source concentration (g/L).