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] |