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. 2021 Aug 30;20:172. doi: 10.1186/s12934-021-01665-5

Table 1.

Major strategies and advancements in achieving and enhancing L-valine production

Host Main engineering strategy Culture condition Performance References
Titer
(g L−1)
Yield
(mol mol−1 glucose)
Productivity
(g L−1 h−1)
C. glutamicum ATCC 13032

Alanine transaminase deactivated,

AHAIS, AHAS and TA overexpressed

3.5 L Fed-batch fermentation

12.5% glucose, 31 °C, 72 h

31.1 0.28 0.43 [11]
C. glutamicum ATCC 13032 Increasing the expression of ptsG 50 mL shake flask fermentation, 4% glucose, 0.5% maltose, 2% acetate, 48 h 11.94 0.21 0.27 [39]
C. glutamicum ATCC 13032 L-threonine dehydratase and ketopantoate hydroxymethyltransferase deactivated. AHAIR, AHAS and DHAD overexpressed 100 mL flask batch cultivation, 4% glucose, 30 °C 48 h 10.7 ND 0.22 [50]
C. glutamicum R Lactate dehydrogenase, alanine transaminase, CoA transferase, phosphotransacetylase, phosphoenolpyruvate carboxylase and acetate kinase deactivated. Variant of AHAIS and AHAS expressed

50 mL (flask) Fed-batch fermentation, 4% glucose, 33 °C, 24 h

(anaerobic condition)

150 0.88 6.25 [66]
C. glutamicum ATCC 13869 L-threonine dehydratase, pyruvate dehydrogenase complex and alanine transaminase deactivated. AHAIR, AHAS and the genes lrp1/brnFE overexpressed 2 L Fed-batch fermentation, 12% glucose, 30 °C, 96 h 51 0.47 0.533 [68]
C. glutamicum R

Leucine dehydrogenase expression

Feedback-resistant muntant AHAS

50 mL (flask) Fed-batch fermentation, 4% glucose, 33 °C, 24 and 48 h (anaerobic condition) 172.2 and 227 0.63 4.09 and 4.72 [65]
C. glutamicum ATCC 13032

Deactivating phosphoenolpyruvate carboxylase and quinone oxidoreductase combined with ALE

AHAIS, AHAS, DHAD and TA overexpressed

50 mL flask batch cultivation, 4% glucose, 30 °C, 72 h 8.9 0.22 0.012 [22]
C. glutamicum VWB-1 Applying multiple random mutagenesis

5 L Fed-batch fermentation,

12% glucose, 31.5 °C 72 h

29.8 ND 0.41 [41]
C. glutamicum ATCC 13032

Random mutagenesis and selection

Transcriptomic and metabolomics analysis

5 L Fed-batch fermentation, 5% glucose, 32 °C, 24 h 44.6 ND ND [46]
Brevibacterium flavum JV16

Alanine transaminase deactivated,

AHAIS, AHAS and TA overexpressed

3.5 L Fed-batch fermentation,

2.5% glucose, 31 °C, 72 h

38.8 0.37 0.53 [11]
Brevibacterium flavumMDV1 Random mutagenesis by UV and Binary ethylenimine; BEI

12 L Fed-batch fermentation,

12.5% glucose, 30 °C, 64 h

68.8 ND 1.07 [12]
E. coli W

L-threonine dehydratase, Isopropyl malate synthase, ketopantoate hydroxymethyltransferase, malate dehydrogenase and pyruvate dehydrogenase phosphofructokinase deactivated (VAMF strain)

AHAIS, AHAS, DHAD, TA and gene lrp/ygaZH overexpressed

100 mL Flask batch cultivation,

2% glucose, 0.3% sodium, 31 °C, 48 h

7.6 ND 0.15 [17]
E. coli W AHAIS, AHAS variant, DHAD, TA and gene lrp/ygaZH overexpressed in VAMF strain

2 L Fed-batch fermentation,

2% glucose,, 31 °C, 55 h

32.2 ND 0.58 [18]
E. coli W

L-threonine dehydratase deactivated

AHAIS, AHAS, DHAD, TA and gene lrp/ygaZH overexpressed

2 L Fed-batch fermentation,

2% glucose,, 31 °C 29.5 h

60.7 0.22 2.06 [19]
E.coli DH5α Heterologous introduction of a feedback-resistant acetolactate acid synthase, exporter, redox cofactor balance, two-stage fed-batch fermentation 5 L Fed-batch fermentation, glucose concentration below 5 g/L, 37℃, 36 h 84 0.41 2.33 [57]
Bacillus subtilis 168 Pyruvate dehydrogenase complex, L-threonine dehydratase, isopropyl malate synthase and transcription factor σ (sigF) deactivated

20 mL Flask batch cultivation

3% sucrose, 1% mannitol, 37 °C 24 h

3.9 ND 0.19 [13]

ND not determined