Skip to main content

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