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Table 1 Strategies for engineering redox homeostasis and its effects on alcohols production

From: Engineering redox homeostasis to develop efficient alcohol-producing microbial cell factories

Strategy

Specific approach

Target product

Main effects

Ref.

Titer

Yield

Productivity

Improving the availability of cofactors

 Fine-tuning of NAD(P)H-dependent gene

Fine-tuining of yjhG and mdlC

1,2,4-Butanetriol

Increased by 71.4%

NR

NR

[4]

Fine-tuning of adhE2

Butanol

Increased from 15 to 18.3 g/L

NR

NR

[31]

 Blocking NADH-competing pathways

Knock out ldh

1,2-Propanediol

Increased from 1.08 to 1.30 g/L anaerobically, from 1.10 to 1.40 g/L microaerobically

Increased by 43% anaerobically, by 67% microaerobically

NR

[19]

Knock out aldA

1,3-Propanediol

Increased from 698.6 to 927.6 mM

Increased from 0.355 to 0.699 mol/mol

Increased by 33%

[34]

Knock out adh, ldh and frd

Butanol

Increased from 141 to 274 mg/L

NR

NR

[20]

Knock out mdh

1,4-Butanediol

Increased from ~3 to ~8 mM

NR

NR

[37]

 Increasing total NAD level

Overexpress pncB

Ethanol

Increased from 11.50 to 28.58 mM

NR

NR

[40]

 Introducing NAD(P)H regeneration systems

Overexpress fdh1

Ethanol

Increased from ~15 to ~175 mM

NR

NR

[21]

Overexpress fdh1

Ethanol

Increased from 52.20 to 117.77 mM

Increased from 0.72 to 1.33 mol/mol

NR

[22]

Overexpress fdh

1,3-Propanediol

NR

Increased by 17.3%

NR

[45]

Overexpress fdh

2,3-Butanediol

Increased from 16.1 to 17.8 g/L

Increased from 82.5 to 91.8%

Increased by 33%

[46]

Activate pyruvate dehydrogenase, fine-tune express fdh1

Butanol

Increased from 5.02 to 6.8 g/L

NR

Increased by 136%

[35]

Overexpress GDP1

Ethanol

Increased from 90 to 100 mM

Increased from 18 to 41%

NR

[49]

Electrically regenerate NADH

Isobutanol

Produced 846 mg/L

NR

NR

[53]

Electrically regenerate NADPH

Isopropanol

Produced 216 mg/L

NR

NR

[55]

Manipulating affinity of redox enzymes for NAD(P)H

 Switching the affinity from one type to another

Mutate XR (NADPH to NADH)

Ethanol

NR

Increased from 0.24 to 0.34 g/g

NR

[63]

Mutate XR (NADPH to NADH)

Ethanol

Increased from 16.7 to 25.3 g/L

Increased from 0.33 to 0.38 g/g

NR

[65]

Introduce NADPH-preferring enzymes in Synechococcus

Butanol

Increased from 6.4 to 29.9 mg/L

NR

NR

[67]

Replace bcd-etfAB with ter

Butanol

Increased from 0.1 to 1.8 g/L

NR

NR

[48]

 Improving affinity for NAD(P)H

Introduce alcohol dehydrogenase II and pyruvate decarboxylase genes from Z. mobilis

Ethanol

Increased from 18 to 750 mM

NR

NR

[18]

Increase affinities of IlvC and AdhA for NADH

Isobutanol

Increased from 1 to 13.4 g/L

Increased from 53 to 100% of the theoretical yield

Increased by 38–88%

[75]

Globally engineering cellular redox balance

  Manipulating respiratory levels

Knock out ubiCA and supply coenzyme Q1

Ethanol

NR

Increased from 0.48 to 0.80 mol/mol aerobically

NR

[78]

 Introducing glutathione

Overexpress gshAB

Butanol

Increased from 10.8 to 14.8 g/L

NR

NR

[84]

 Engineering redox-sensitive transcription factor Rex

Inactivate rex

Ethanol, Butanol

Increased from ~20 to ~120 mM and increased from 60 to 120 mM, respectively

NR

NR

[87]

  1. NR not reported