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Table 3 Prokaryotic microorganisms and their genetic modifications for the HA production

From: Genetic basis for hyper production of hyaluronic acid in natural and engineered microorganisms

Microorganism Genetic modification Substrate concentration (g/L) Production (g/L) Yield YP/S (g/g) Productivity (g/L/h) Molecular weight (MDa) Reference
Lactococcus lactis BCRC 12312 Operon containing HA synthase (HasA) of S. equi subsp. zooepidemicus Glucose: 0.1 0.08 0.8a 0.0022b NR [62]
Lactococcus lactis BCRC 12312 Operon containing HA synthase (HasA) and UDP-GlcDH (HasB) of S. equi subsp. zooepidemicus Glucose: 0.1 0.65 6.5a 0.018b NR [62]
Lactococcus lactis NZ9000 Expression of HA synthase and UDP-glucose-6-dehydrogenase of Streptococcus zooepidemicus Fed batch of glucose: 5 and fed batch of lactose: 20 0.12 NR NR 0.879 [65]
0.59 NR NR 0.569
Lactococcus lactis NZ9000 (SJR2) has operon of Streptococcus zooepidemicus (co-expressing HasA and HasB genes only) Glucose: 15 0.107 (in static flask experiments) 0.007a 0.0178 NR [61]
Glucose: 25 0.068 (in static flask experiments) 0.002a 0.0113 NR
Lactococcus lactis NZ9000 (SJR3) has operon of Streptococcus zooepidemicus (co-expressing HasA, HasB, and HasC genes) Glucose: 10 0.234 (in static flask experiments) 0.023a 0.039 NR
Glucose: 25 0.154 (in static flask experiments) 0.006a 0.257 NR
Lactococcus lactis NZ9000 (SJR2) has operon of Streptococcus zooepidemicus (co-expressing HasA and HasB genes only) Glucose: 10 0.123 0.012 0.005b NR [63]
Lactococcus lactis NZ9000 (SJR3) has operon of Streptococcus zooepidemicus (co-expressing HasA, HasB, and HasC genes) Glucose: 10 0.43 0.041 (YP/S) 0.0179b NR [63]
Lactococcus lactis NZ9000 (SJR6) Three has operon genes (HasA, HasB and glmU) from S. zooepidemicus Glucose: 10 0.595 0.09 g/g (YP/S) 0.0248b NR
L. lactis NZ9000 L. lactis carrying HasA- HasB gene in nisRK region Glucose: 10 0.14 0.014a 0.0117 4.3 [77]
VRJ2AB
Lactococcus lactis NZ9000 VRJ3ABC L. lactis carrying HasA- HasB- HasC gene in the nisRK region Glucose: 10 0.68 0.068 0.0567 3.49 [77]
Enterococcus faecalis OGlRF Transposon 916 insertional mutagenesis THY broth 0.002-0.69 ND ND ND [64]
Was subcloned into a plasmid shuttle vector (pAT19 and pPD41)
Corynebacterium glutamicum ATCC 13032 pJH174.1 HasA expression MEK700 with glucose: 40 Between 0.3 and 0.4 0.017 ~0.003b >1.4 [87]
CGXII with glucose: 40 ~1.0 0.023 ~0,008b <0.27
Corynebacterium glutamicum ATCC 13032 pJH181.3 HasA and HasC coexpression MEK700 with glucose: 40 Between 0.3 and 0.4 0.016 ~0.003b >1.4
CGXII with glucose: 40 Between 1.0 and 1.3 0.025 ~0.01b <0.27
Corynebacterium glutamicum ATCC 13032 pJH182.1 HasA and vgb (bacterial haemoglobin from Vitreoscilla sp.) coexpression MEK700 with glucose: 40 Between 0.1 and 0.2 0.075 ~0.001b >1.4
CGXII with glucose: 40 ~0.8 0.014 ~0.007b <0.27
Corynebacterium glutamicum ATCC 13032 pJH183.2 HasA, HasC and HasB coexpression MEK700 with glucose: 40 Between 0.3 and 0.4 0.017 ~0.003b >0.67
CGXII with glucose: 40 ~1.3 0.027 ~0.01b <0.27
Corynebacterium glutamicum ATCC 13032 pJH195.2 HasA and glmU (from Pseudomonas putida KT2440) coexpression MEK700 with glucose: 40 ~0.3 0.014 ~0.003b >1.4
CGXII with glucose: 40 Between 1.0 and 1.3 0.026 ~0.01b <0.27
Corynebacterium glutamicum ATCC 13032 pJH196.2 HasA, HasC and glmU coexpression MEK700 with glucose: 40 Between 0.3 and 0.4 0.017 ~0.003b >1.4
CGXII with glucose: 40 ~1.2 0.027 ~0.01b <0.27
Corynebacterium glutamicum ATCC 13032 pJH197.1 HasA, glmU (from Pseudomonas putida KT2440) and HasC coexpression MEK700 with glucose: 40 <0.3 0.013 ~0.003b >0.67
CGXII with glucose: 40 Between 1.0 and 1.3 0.025 ~ ~0.01b <0.27
Agrobacterium sp ATCC31749 Coexpression of HA synthase from Pasteurella multocida, and UDP-glucose dehydrogenase from Escherichia coli Sucrose: ~42.8, Lactose: 3.4 ~3.0 0.0645a 0.5b 1.56 [47]
Agrobacterium sp LTU261 Coexpression of HA synthase from Pasteurella multocida, and UDP-glucose dehydrogenase from Escherichia coli ~2.3 0.0495a 0.38b 2.17
Agrobacterium sp LTU265 Coexpression of HA synthase from Pasteurella multocida, and UDP-glucose dehydrogenase from Escherichia coli ~2.4 0.06a 0.4b 0.72
Escherichia coli JM109 Co-expression of HA synthase from Pasteurella Terrific Broth/feeding medium contained 0.50 glucose (after feeding: glucose: 50) (Bioreactor) 2.0 0.027 0.0127 NR [48]
3.8 (fed-batch fermentation process in a 1 L
Multocida and uridine diphosphate-glucose dehydrogenase from E. coli K5 strain Bioreactor)
Escherichia coli OP50 CPS1 cDNA from C. neoformans NR NR NR ~4 ng/hr/µg protein NR [39]
Escherichia coli x1448 Transposon 916 insertional mutagenesis was subcloned into a plasmid shuttle vector (pPD41, pPD41Δ4, pPD41 Δ5 and pPD41 Δ6) THY broth 0.002–0.08 NR NR NR [64]
Escherichia coli K12 MG1655 sseAB Gene of sse HasA with identical protein sequence of seHAS from Streptococcus equisimilis Glucose: 10 (fed batch) 0.155 (24 h) 0.0155 (24 h)a 0.0065 (24 h) 0.38 (24 h) [69]
0.196 (48 h) 0.0196 (48 h)a 0.0041 (48 h) 0.5 M (48 h)
0.202 (72 h) 0.0202 (72 h)a 0.0028 (72 h) 1.7 (72 h)
Escherichia coli K12 MG1655 sseABC Gene of sse HasA with identical protein sequence of seHAS from Streptococcus equisimilis Glucose: 10 (fed batch) 0.148 (48 h) 0.0148a 0.0031 0.39 [69]
Escherichia coli C0 Top10/(pMBAD-sseABC, pHACM-blank) Two plasmids and the chromosomal copies of wildtype
rpoD and rpoS.
Glucose: 10 (fed batch) 0.405 0.0405a 0.008 NR [92]
Escherichia coli C1 Top10/(pMBAD-sseABC) Used as the control strain in library screening, harboring a single plasmid and the chromosomal copies of wild type rpoD and rpoS Glucose: 10 (fed batch) 0.510 0.0510a 0.0106 NR [92]
Escherichia coli D72 Top10/(pMBAD-sseABC, pHACM-rpoDM72) Extra copy of mutant rpoD or rpoS in the pHACM plasmid Glucose: 10 (fed batch) 0.561 0.0561a 0.0117 NR [92]
Escherichia coli D2
Top10/(pMBAD-sseABC, pHACM-rpoDM2)
Extra copy of mutant rpoD or rpoS in the pHACM plasmid Glucose: 10 (fed batch) 0.548 0.0548a 0.0114 NR [92]
Escherichia coli S47 Top10/(pMBAD-sseABC, pHACM-rpoSM47) Extra copy of mutant rpoD or rpoS in the pHACM
plasmid
Glucose: 10 (fed batch) 0.479 0.0479a 0.00998 NR [92]
Escherichia coli D0 Top10/(pMBAD-sseABC, pHACM-rpoD) With an extra copy of unmutated rpoD on pHACM; Glucose: 10 (fed batch) 0.425 0.0425a 0.009 NR [92]
Escherichia coli S0 Top10/(pMBAD-sseABC, pHACM-rpoS) With an extra copy of unmutated rpoS on pHACM; Fed batch of glucose: 10 0.696 0.0696a 0.015 NR [92]
Streptomyces albulus pJHA4 hasA gene from 29 Streptococcus zooepidemicus Fed batch of glucose glucose: 50 6.2 0.062a 0.886b 2 [70]
Bacillus subtilis Operon containing HA synthase (HasA) of Streptococcus, tuaD (hasB) Fed batch rate of sucrose: 2 NR 1 NR 4.0 [71]
Bacillus subtilis Operon containing HA synthase (HasA) of Streptococcus, tuaD (hasB) and Vitreoscilla hemoglobin (VHb) Glucose: 10 1.8 0.18a 0.6b NR [64]
Bacillus subtilis Operon containing HA synthase (HasA) of Streptococcus and tuaD controlled by inductive promoters Glucose: 10 6.8 0.68a 0.34b 6.5 [72]
  1. NR not reported
  2. aCalculated from the values reported by the authors of the maximum production of HA (P) and the consumed substrate (S), defined as Yield = P/S
  3. bCalculated from the values reported by the authors of the maximum production of HA (P) and the cultivation time to obtain this production (t), defined as Productivity = P/t