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. Author manuscript; available in PMC: 2022 Dec 12.
Published in final edited form as: Curr Opin Chem Biol. 2020 Nov 14;59:202–204. doi: 10.1016/j.cbpa.2020.10.006

Corrigendum to “Rewiring yeast metabolism to synthesize products beyond ethanol” [Curr Opin Chem Biol 59 (December 2020) 182–192]

Francesca V Gambacorta 1,2, Joshua J Dietrich 1,2, Qiang Yan 1,3, Brian F Pfleger 1,2,3,4,#
PMCID: PMC9744135  NIHMSID: NIHMS1852750  PMID: 33199243

The authors regret to inform that the presented values in Table 1 are incorrect in the published version. The corrected values are provided below. The authors would like to apologize for any inconvenience caused.

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 0.14a < 0.5 Glucose, minimal medium, batch, flask, aerobic
Pyruvate 0.007a < 0.5
[25] ✓ ✓ ✓ 2,3-Butanediol 0.28 96.2 Glucose, YP medium, fed-batch, bioreactor, aerobic
Glycerol 0.09a >30c
Acetoin 0.01a ~5 c
[33] ✓ ✓ 2,3-Butanediol 0.407 72.91 Glucose, YP medium, fed-batch, flask, aerobic
Acetoin 0.01a 1.38
[34] ✓ ✓ 2,3-Butanediol 0.359 32.31c Glucose + ethanol, minimal media, batch, bioreactor, oxygen-limited
Glycerol 0.069 6.21c
Acetoin 0.052 4.68c
[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 0.006a 2.3
[36] ✓ ✓ ✓ ✓ 2,3-Butanediol 0.462 108.6 Glucose, YP medium, fed-batch, bioreactor, full aeration followed by oxygen limitation
Acetoin 0.02a 4.6
Acetate 0.0004a 0.1
[27] ✓ ✓ ✓ 2,3-Butanediol 0.27 81.0 Glucose, synthetic defined medium, fed-batch, flask, mild aerobic
Glycerol 0.239a 71.8
Succinate 0.013a 4.0
[72] ✓ ✓ n-Butanol 0.012 0.130 Glucose + pantothenate, SMD medium, flask, semi-anaerobic
Ethanol 0.10 ~1c
Glycerol 0.17 ~2c
[43] ✓ ✓ ✓ Isobutanol 0.0074a b Glucose, SMG medium + Tween-80 + ergosterol, batch, serum bottle, microaerobic
Ethanol 0.033a b
Glycerol 0.26a b
Pyruvate 0.02a b
2,3-butanediol 0.325a b
Dihydroxyisovalerate 0.05a b
Isobutyrate 0.03a 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
Glycerol b b
[42] ✓ ✓ ✓ Malic acid 0.31a 59 Glucose, synthetic medium, batch, flask, aerobic
Succinate 0.04a 8
Glycerol 0.13a 25
Pyruvate 0.02a 3
Fumarate 0.01a 2
[54] ✓ ✓ ✓ Succinic acid 0.044a 2.2 Glucose + formate, mineral salt medium, deep-well plate, microaerobic
Pyruvate 0.364a 18.2
Malate 0.022a 1.1
Glycerol 0.076a 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
Ethanol 0.02a 2.6
[69] ✓ ✓ ✓ Lactic acid 0.43a 7.8 2-stage sugar consumption (ethanol then xylose), YP medium, batch, bioreactor, aerobic followed by microaerophilic
Acetate 0.16a 3c
Xylitol 0.01a 0.17c
[70] ✓ ✓ Lactic acid 0.67 60 Xylose, YP medium, batch, flask, aerobic
Ethanol 0.01a <1
Xylitol 0.01a <1
Glycerol 0.01a <1
Acetate 0.01a <1
[68] ✓ ✓ ✓ ✓ 2,3-Butanediol 0.46a 96.8 Xylose + glucose, YP medium, fed-batch, bioreactor, microaerobic
Glycerol 0.11a 23.3
Ethanol 0.08a 16.3
Xylitol 0.03a 5.9
[73] ✓ ✓ ✓ 2,3-Butanediol 0.26a 43.6 Xylose + glucose, YP medium, fed-batch, bioreactor, microaerobic
Glycerol 0.26a 45
Xylitol 0.03a 4.7
[63] ✓ ✓ Isobutanol 0.026a 2.6 Xylose, nutrient-rich Verduyn medium, fed-batch, bioreactor, aerobic
Ethanol 0.275a ~27.5 c
Glycerol 0.10a ~10 g/Lc
[62] ✓ ✓ Isobutanol 0.0196 3.10 Xylose, synthetic medium, fed-batch, conical tube, semi-anaerobic
2-Methyl-1-butanol 0.0053 0.79
Ethanol 0.32a <50c
Glycerol b b
[67] ✓ ✓ 1,2-Propanediol 0.129 4.3 Glycerol, YP medium, batch, bioreactor, aerobic
Ethanol ~0a ~0c
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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).

Acknowledgements:

This material is based upon work supported in part by the Great Lakes Bioenergy Research Center, U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research under Award Number DE-SC0018409 and in part by the Center for Bioenergy and Bioproducts Innovation, U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research under Award Number DE-SC0018420). Any opinions, findings, and conclusions or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the U.S. Department of Energy

Bibliography

  • 1.Synthetic biology toolkits and applications in Saccharomyces cerevisiae. Biotechnol Adv 2018, 36:1870–1881. [DOI] [PubMed] [Google Scholar]
  • 2.Recent advances in metabolic engineering of Saccharomyces cerevisiae: New tools and their applications. Metab Eng 2018, 50:85–108. [DOI] [PubMed] [Google Scholar]
  • 3.Salari R, Salari R: Investigation of the best Saccharomyces cerevisiae growth condition. Electronic physician 2017, 9:3592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.McIlwain SJ, Peris D, Sardi M, Moskvin OV, Zhan F, Myers KS, Riley NM, Buzzell A, Parreiras LS, Ong IM, et al. : Genome Sequence and Analysis of a Stress-Tolerant, Wild-Derived Strain of Saccharomyces cerevisiae Used in Biofuels Research. G3: Genes, Genomes, Genetics 2016, 6:1757–1766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Jullesson D, David F, Pfleger B, Nielsen J: Impact of synthetic biology and metabolic engineering on industrial production of fine chemicals. Biotechnol Adv 2015, 33:1395–1402. [DOI] [PubMed] [Google Scholar]
  • 6.Hong K-K, Nielsen J: Metabolic engineering of Saccharomyces cerevisiae: a key cell factory platform for future biorefineries. Cell Mol Life Sci 2012, 69:2671–2690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Mehrer CR, Incha MR, Politz MC, Pfleger BF: Anaerobic Production of Medium-Chain Fatty Alcohols via a β-Reduction Pathway. Metab Eng 2018, 48:63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Vemuri GN, Eiteman MA, McEwen JE, Olsson L, Nielsen J: Increasing NADH oxidation reduces overflow metabolism in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 2007, 104:2402–2407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Kayikci Ö, Nielsen J: Glucose repression in Saccharomyces cerevisiae. FEMS Yeast Res 2015, 15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. de Alteriis E, Cartenì F, Parascandola P, Serpa J, Mazzoleni S: Revisiting the Crabtree/Warburg effect in a dynamic perspective: a fitness advantage against sugar-induced cell death. Cell Cycle 2018, 17:688–701. *Review discussing and interpreting the proposed mechanisms and theories behind the Crabtree-Warburg effect. Detailing the short/long term effect and sugar-induced cell death.
  • 11.Pfeiffer T, Morley A: An evolutionary perspective on the Crabtree effect. Front Mol Biosci 2014, 1:17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Nilsson A, Nielsen J: Metabolic Trade-offs in Yeast are Caused by F1F0-ATP synthase. Sci Rep 2016, 6:22264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Sánchez BJ, Zhang C, Nilsson A, Lahtvee P-J, Kerkhoven EJ, Nielsen J: Improving the phenotype predictions of a yeast genome-scale metabolic model by incorporating enzymatic constraints. Mol Syst Biol 2017, 13:935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Flikweert MT, Van Der Zanden L, Janssen WM, Steensma HY, Van Dijken JP, Pronk JT: Pyruvate decarboxylase: an indispensable enzyme for growth of Saccharomyces cerevisiae on glucose. Yeast 1996, 12:247–257. [DOI] [PubMed] [Google Scholar]
  • 15.Ida Y, Furusawa C, Hirasawa T, Shimizu H: Stable disruption of ethanol production by deletion of the genes encoding alcohol dehydrogenase isozymes in Saccharomyces cerevisiae. J Biosci Bioeng 2012, 113:192–195. [DOI] [PubMed] [Google Scholar]
  • 16.Oud B, Flores C-L, Gancedo C, Zhang X, Trueheart J, Daran J-M, Pronk JT, van Maris AJA: An internal deletion in MTH1 enables growth on glucose of pyruvate-decarboxylase negative, non-fermentative Saccharomyces cerevisiae. Microb Cell Fact 2012, 11:131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.van Rossum HM, Kozak BU, Niemeijer MS, Duine HJ, Luttik MAH, Boer VM, Kötter P, Daran J-MG, van Maris AJA, Pronk JT: Alternative reactions at the interface of glycolysis and citric acid cycle in Saccharomyces cerevisiae. FEMS Yeast Res 2016, 16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Zhang Y, Liu G, Engqvist MKM, Krivoruchko A, Hallström BM, Chen Y, Siewers V, Nielsen J: Adaptive mutations in sugar metabolism restore growth on glucose in a pyruvate decarboxylase negative yeast strain. Microb Cell Fact 2015, 14:116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Liu H, Fan J, Wang C, Li C, Zhou X: Enhanced β-Amyrin Synthesis in Saccharomyces cerevisiae by Coupling An Optimal Acetyl-CoA Supply Pathway. J Agric Food Chem 2019, 67:3723–3732. *Authors generated a strain with a high flux towards cytosolic acetyl-CoA for the production of β-amyrin at high titers (279.0 +/− 13.0 mg/L) in a fed-batch system. This was achieved by combining multiple heterologous acetyl-CoA supply routes and eliminating competing pathways in a β-amyrin producing strain.
  • 20.van Rossum HM, Kozak BU, Pronk JT, van Maris AJA: Engineering cytosolic acetyl-coenzyme A supply in Saccharomyces cerevisiae: Pathway stoichiometry, free-energy conservation and redox-cofactor balancing. Metab Eng 2016, 36:99–115. [DOI] [PubMed] [Google Scholar]
  • 21.Gancedo JM: The early steps of glucose signalling in yeast. FEMS Microbiol Rev 2008, 32:673–704. [DOI] [PubMed] [Google Scholar]
  • 22.Kim J-H, Roy A, Jouandot D 2nd, Cho KH: The glucose signaling network in yeast. Biochim Biophys Acta 2013, 1830:5204–5210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Klein CJ, Olsson L, Nielsen J: Glucose control in Saccharomyces cerevisiae: the role of Mig1 in metabolic functions. Microbiology 1998, 144 (Pt 1):13–24. [DOI] [PubMed] [Google Scholar]
  • 24.Habegger L, Rodrigues Crespo K, Dabros M: Preventing Overflow Metabolism in Crabtree-Positive Microorganisms through On-Line Monitoring and Control of Fed-Batch Fermentations. Fermentation 2018, 4:79. [Google Scholar]
  • 25.Kim S-J, Seo S-O, Jin Y-S, Seo J-H: Production of 2,3-butanediol by engineered Saccharomyces cerevisiae. Bioresour Technol 2013, 146:274–281. [DOI] [PubMed] [Google Scholar]
  • 26.Van Maris AJA, Geertman J-MA, Vermeulen A, Groothuizen MK, Winkler AA, Piper MDW, Van Dijken JP, Pronk JT: Directed evolution of pyruvate decarboxylase-negative Saccharomyces cerevisiae, yielding a C2-independent, glucose-tolerant, and pyruvate-hyperproducing yeast. Appl Environ Microbiol 2004, 70:159–166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. Ishii J, Morita K, Ida K, Kato H, Kinoshita S, Hataya S, Shimizu H, Kondo A, Matsuda F: A pyruvate carbon flux tugging strategy for increasing 2,3-butanediol production and reducing ethanol subgeneration in the yeast. Biotechnol Biofuels 2018, 11:180. **Demonstrated that NAD+ regeneration through 2,3-butanediol production can replace ethanol fermentation in an evolved Pdc− S. cerevisiae strain. The best strain in the study produced 81 g/L of 2,3-butanediol by pulling pyruvate flux to 2-acetolactate, the first metabolite in the 2,3-butanediol pathway, by heterologously expressing an acetolactate synthase variant from Lactobacillus plantarum and co-expressing an endogenous butanediol dehydrogenase.
  • 28. Yu T, Zhou YJ, Huang M, Liu Q, Pereira R, David F, Nielsen J: Reprogramming Yeast Metabolism from Alcoholic Fermentation to Lipogenesis. Cell 2018, 174:1549–1558.e14. **Yu and co-workers rewired yeast metabolism to enhance carbon flux to free fatty acids instead of ethanol by rational metabolic engineering and ALE in a design-build-evolve-test cycle. Free fatty acids were produced at high titers of 25.0 g/L in fed-batch fermentation by enhancing carbon flux to cytosolic acetyl-CoA, increasing the NADPH supply, balancing ATP levels, eliminating ethanol fermentation, and relieving the Crabtree-effect.
  • 29.Martinez-Ortiz C, Carrillo-Garmendia A, Correa-Romero BF, Canizal-García M, González-Hernández JC, Regalado-Gonzalez C, Olivares-Marin IK, Madrigal-Perez LA: SNF1 controls the glycolytic flux and mitochondrial respiration. Yeast 2019, 36:487–494. [DOI] [PubMed] [Google Scholar]
  • 30.Rosas Lemus M, Roussarie E, Hammad N, Mougeolle A, Ransac S, Issa R, Mazat J-P, Uribe-Carvajal S, Rigoulet M, Devin A: The role of glycolysis-derived hexose phosphates in the induction of the Crabtree effect. J Biol Chem 2018, 293:12843–12854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Baek S-H, Kwon EY, Kim S-Y, Hahn J-S: GSF2 deletion increases lactic acid production by alleviating glucose repression in Saccharomyces cerevisiae. Sci Rep 2016, 6:34812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Vicente RL, Spina L, Gómez JPL, Dejean S, Parrou J-L, François JM: Trehalose-6-phosphate promotes fermentation and glucose repression in Saccharomyces cerevisiae. Microb Cell Fact 2018, 5:444–459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Kim S, Hahn J-S: Efficient production of 2,3-butanediol in Saccharomyces cerevisiae by eliminating ethanol and glycerol production and redox rebalancing. Metab Eng 2015, 31:94–101. [DOI] [PubMed] [Google Scholar]
  • 34.Kim J-W, Seo S-O, Zhang G-C, Jin Y-S, Seo J-H: Expression of Lactococcus lactis NADH oxidase increases 2,3-butanediol production in Pdc-deficient Saccharomyces cerevisiae. Bioresour Technol 2015, 191:512–519. [DOI] [PubMed] [Google Scholar]
  • 35.Kim J-W, Kim J, Seo S-O, Kim KH, Jin Y-S, Seo J-H: Enhanced production of 2,3-butanediol by engineered Saccharomyces cerevisiae through fine-tuning of pyruvate decarboxylase and NADH oxidase activities. Biotechnol Biofuels 2016, 9:1–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Kim J-W, Lee Y-G, Kim S-J, Jin Y-S, Seo J-H: Deletion of glycerol-3-phosphate dehydrogenase genes improved 2,3-butanediol production by reducing glycerol production in pyruvate decarboxylase-deficient Saccharomyces cerevisiae. J Biotechnol 2019, 304:31–37. [DOI] [PubMed] [Google Scholar]
  • 37.Ida Y, Hirasawa T, Furusawa C, Shimizu H: Utilization of Saccharomyces cerevisiae recombinant strain incapable of both ethanol and glycerol biosynthesis for anaerobic bioproduction. Appl Microbiol Biotechnol 2013, 97:4811–4819. [DOI] [PubMed] [Google Scholar]
  • 38.Hirasawa T, Ida Y, Furuasawa C, Shimizu H: Potential of a Saccharomyces cerevisiae recombinant strain lacking ethanol and glycerol biosynthesis pathways in efficient anaerobic bioproduction. Bioengineered 2014, 5:123–128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.van Maris AJA, Winkler AA, Porro D, van Dijken JP, Pronk JT: Homofermentative lactate production cannot sustain anaerobic growth of engineered Saccharomyces cerevisiae: possible consequence of energy-dependent lactate export. Appl Environ Microbiol 2004, 70:2898–2905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Baek S-H, Kwon EY, Kim YH, Hahn J-S: Metabolic engineering and adaptive evolution for efficient production of D -lactic acid in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 2015, 100:2737–2748. [DOI] [PubMed] [Google Scholar]
  • 41.Zhong W, Yang M, Mu T, Wu F, Hao X, Chen R, Sharshar MM, Thygesen A, Wang Q, Xing J: Systematically redesigning and optimizing the expression of D-lactate dehydrogenase efficiently produces high-optical-purity D-lactic acid in Saccharomyces cerevisiae. Biochem Eng J 2019, 144:217–226. [Google Scholar]
  • 42.Zelle RM, de Hulster E, van Winden WA, de Waard P, Dijkema C, Winkler AA, Geertman J-MA, van Dijken JP, Pronk JT, van Maris AJA: Malic Acid Production by Saccharomyces cerevisiae: Engineering of Pyruvate Carboxylation, Oxaloacetate Reduction, and Malate Export. Appl Environ Microbiol 2008, 74:2766–2777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Milne N, Wahl SA, van Maris AJA, Pronk JT, Daran JM: Excessive by-product formation: A key contributor to low isobutanol yields of engineered strains. Metab Eng Commun 2016, 3:39–51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Shi A, Zhu X, Lu J, Zhang X, Ma Y: Activating transhydrogenase and NAD kinase in combination for improving isobutanol production. Metab Eng 2013, 16:1–10. [DOI] [PubMed] [Google Scholar]
  • 45.Ida K, Ishii J, Matsuda F, Kondo T, Kondo A: Eliminating the isoleucine biosynthetic pathway to reduce competitive carbon outflow during isobutanol production by Saccharomyces cerevisiae. Microb Cell Fact 2015, 14:62. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Wang Z, Gao C, Wang Q, Liang Q, Qi Q: Production of pyruvate in Saccharomyces cerevisiae through adaptive evolution and rational cofactor metabolic engineering. Biochem Eng J 2012, 67:126–131. [Google Scholar]
  • 47.Matsuda F, Ishii J, Kondo T, Ida K, Tezuka H, Kondo A: Increased isobutanol production in Saccharomyces cerevisiae by eliminating competing pathways and resolving cofactor imbalance. Microb Cell Fact 2013, 12:119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Feng R, Li J, Zhang A: Improving isobutanol titers in Saccharomyces cerevisiae with over-expressing NADPH-specific glucose-6-phosphate dehydrogenase (Zwf1). Ann Microbiol 2017, 67:785–791. [Google Scholar]
  • 49.Bastian S, Liu X, Meyerowitz JT, Snow CD, Chen MMY, Arnold FH: Engineered ketol-acid reductoisomerase and alcohol dehydrogenase enable anaerobic 2-methylpropan-1-ol production at theoretical yield in Escherichia coli. Metab Eng 2011, 13:345–352. [DOI] [PubMed] [Google Scholar]
  • 50.Naghshbandi MP, Tabatabaei M, Aghbashlo M, Gupta VK, Sulaiman A, Karimi K, Moghimi H, Maleki M: Progress toward improving ethanol production through decreased glycerol generation in Saccharomyces cerevisiae by metabolic and genetic engineering approaches. Renewable Sustainable Energy Rev 2019, 115:109353. [Google Scholar]
  • 51.Jouhten P, Rintala E, Huuskonen A, Tamminen A, Toivari M, Wiebe M, Ruohonen L, Penttilä M, Maaheimo H: Oxygen dependence of metabolic fluxes and energy generation of Saccharomyces cerevisiae CEN.PK113-1A. BMC Syst Biol 2008, 2:60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Nevoigt E, Stahl U: Osmoregulation and glycerol metabolism in the yeast Saccharomyces cerevisiae. FEMS Microbiol Rev 1997, 21:231–241. [DOI] [PubMed] [Google Scholar]
  • 53.Yan D, Wang C, Zhou J, Liu Y, Yang M, Xing J: Construction of reductive pathway in Saccharomyces cerevisiae for effective succinic acid fermentation at low pH value. Bioresour Technol 2014, 156:232–239. [DOI] [PubMed] [Google Scholar]
  • 54.Zahoor A, Küttner FTF, Blank LM, Ebert BE: Evaluation of pyruvate decarboxylase-negative strains for the production of succinic acid. Eng Life Sci 2019, 19:711–720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Papapetridis I, Goudriaan M, Vázquez Vitali M, de Keijzer NA, van den Broek M, van Maris AJA, Pronk JT: Optimizing anaerobic growth rate and fermentation kinetics in Saccharomyces cerevisiae strains expressing Calvin-cycle enzymes for improved ethanol yield. Biotechnol Biofuels 2018, 11:17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Guadalupe Medina V, Almering MJH, van Maris AJA, Pronk JT: Elimination of glycerol production in anaerobic cultures of a Saccharomyces cerevisiae strain engineered to use acetic acid as an electron acceptor. Appl Environ Microbiol 2010, 76:190–195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Venayak N, von Kamp A, Klamt S, Mahadevan R: MoVE identifies metabolic valves to switch between phenotypic states. Nat Commun 2018, 9:5332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Flux controlling technology for central carbon metabolism for efficient microbial bio-production. Curr Opin Biotechnol 2020, 64:169–174. [DOI] [PubMed] [Google Scholar]
  • 59.Lalwani MA, Zhao EM, Avalos JL: Current and future modalities of dynamic control in metabolic engineering. Curr Opin Biotechnol 2018, 52:56–65. [DOI] [PubMed] [Google Scholar]
  • 60.Tan SZ, Manchester S, Prather KLJ: Controlling Central Carbon Metabolism for Improved Pathway Yields in Saccharomyces cerevisiae. ACS Synth Biol 2016, 5:116–124. [DOI] [PubMed] [Google Scholar]
  • 61. Zhao EM, Zhang Y, Mehl J, Park H, Lalwani MA, Toettcher JE, Avalos JL: Optogenetic regulation of engineered cellular metabolism for microbial chemical production. Nature 2018, 555:683–687. **This study combines two circuits, OptoEXP (light-induced) and OptoINVRT (dark-induced), to enable a switch between a cellular growth phase with ethanol fermentation and an isobutanol production phase. Through optimizing the light schedule and co-expressing a mitochondrial compartmentalized isobutanol pathway, the study demonstrated 8.49 g/L isobutanol production in a fed-batch fermentation, the highest reported isobutanol titer produced by yeast to date.
  • 62.Zhang Y, Lane S, Chen J-M, Hammer SK, Luttinger J, Yang L, Jin Y-S, Avalos JL: Xylose utilization stimulates mitochondrial production of isobutanol and 2-methyl-1-butanol in Saccharomyces cerevisiae. Biotechnol Biofuels 2019, 12:1–15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63. Lane S, Zhang Y, Yun EJ, Ziolkowski L, Zhang G, Jin Y-S, Avalos JL: Xylose assimilation enhances the production of isobutanol in engineered Saccharomyces cerevisiae. Biotechnol Bioeng 2020, 117:372–381. *This study demonstrated the advantages of using xylose as a carbon source over other sugars like glucose and galactose. In a fermentation with a strain harboring the mitochondrial compartmentalized pathway, more isobutanol and less ethanol was produced compared to the other sugars.
  • 64.Jin Y-S, Laplaza JM, Jeffries TW: Saccharomyces cerevisiae engineered for xylose metabolism exhibits a respiratory response. Appl Environ Microbiol 2004, 70:6816–6825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.Kwak S, Jo JH, Yun EJ, Jin Y-S, Seo J-H: Production of biofuels and chemicals from xylose using native and engineered yeast strains. Biotechnol Adv 2019, 37:271–283. [DOI] [PubMed] [Google Scholar]
  • 66.Sato TK, Tremaine M, Parreiras LS, Hebert AS, Myers KS, Higbee AJ, Sardi M, McIlwain SJ, Ong IM, Breuer RJ, et al. : Directed Evolution Reveals Unexpected Epistatic Interactions That Alter Metabolic Regulation and Enable Anaerobic Xylose Use by Saccharomyces cerevisiae. PLoS Genet 2016, 12:e1006372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67.Islam Z-U, Klein M, Aßkamp MR, Ødum ASR, Nevoigt E: A modular metabolic engineering approach for the production of 1,2-propanediol from glycerol by Saccharomyces cerevisiae. Metab Eng 2017, 44:223–235. [DOI] [PubMed] [Google Scholar]
  • 68.Kim SJ, Sim HJ, Kim JW, Lee YG, Park YC, Seo JH: Enhanced production of 2,3-butanediol from xylose by combinatorial engineering of xylose metabolic pathway and cofactor regeneration in pyruvate decarboxylase-deficient Saccharomyces cerevisiae. Bioresour Technol 2017, 245. [DOI] [PubMed] [Google Scholar]
  • 69.Novy V, Brunner B, Nidetzky B: l -Lactic acid production from glucose and xylose with engineered strains of Saccharomyces cerevisiae : aeration and carbon source influence yields and productivities. Microb Cell Fact 2018, 17:1–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Turner TL, Zhang G-C, Kim SR, Subramaniam V, Steffen D, Skory CD, Jang JY, Yu BJ, Jin Y-S: Lactic acid production from xylose by engineered Saccharomyces cerevisiae without PDC or ADH deletion. Appl Microbiol Biotechnol 2015, 99:8023–8033. [DOI] [PubMed] [Google Scholar]
  • 71. Dai Z, Huang M, Chen Y, Siewers V, Nielsen J: Global rewiring of cellular metabolism renders Saccharomyces cerevisiae Crabtree negative. Nat Commun 2018, 9:3059. **In this study, a Crabtree-negative S. cerevisiae was created by combining ALE with a rationally designed acetyl-CoA synthesis pathway (Po and Pta) to reduce the growth defect seen in Pdc− strains grown on glucose. More specifically, the evolved mutant carried mutations in MED2, which encodes a component of the RNA polymerase II mediator complex, and GPD1, which encodes an enzyme in glycerol biosynthesis. Using reverse engineering they generated a strain that had a growth rate of 0.218 h−1, which is the highest reported for a Pdc− strain grown on glucose medium.
  • 72.Schadeweg V, Boles E: n-Butanol production in Saccharomyces cerevisiae is limited by the availability of coenzyme A and cytosolic acetyl-CoA. Biotechnol Biofuels 2016, 9:44. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73.Production of 2,3-butanediol from xylose by engineered Saccharomyces cerevisiae. J Biotechnol 2014, 192:376–382. [DOI] [PubMed] [Google Scholar]
  • 74.Abbott DA, Zelle RM, Pronk JT, van Maris AJA: Metabolic engineering of Saccharomyces cerevisiae for production of carboxylic acids: current status and challenges. FEMS Yeast Res 2009, 9:1123–1136. [DOI] [PubMed] [Google Scholar]

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