The P170 expression system enhances hyaluronan molecular weight and production in metabolically-engineered Lactococcus lactis

Hyaluronan production and molecular weight is enhanced in pathway-engineered strains of lactate dehydrogenase-deficient Lactococcus lactis

“…Hyaluronic acid (HA) production by metabolically-engineered recombinant organisms is being studied intensively, due to potential advantages over current commercial sources. Some of the recombinant GRAS organisms used for production of HA include Escherichia coli ( Mao et al, 2009 , Yu and Stephanopoulos, 2008 ), Bacillus subtilis ( Chien and Lee, 2007a , Jia et al, 2013 , Widner et al, 2005 ), Agrobacterium ( Mao and Chen, 2007 ) and Lactococcus lactis ( Badle et al, 2014 , Chauhan et al, 2014 , Chien and Lee, 2007b , Hmar et al, 2014 , Prasad et al, 2010 , Sheng et al, 2009 ). A comparison of various recombinant bacterial strains used for HA production, in terms of HA concentration, yield and molecular weight (based on the standards used) is given in Table 1 .…”

“…However, many studies have demonstrated that incorporation and expression of heterologous hasA alone results in low HA production. Co-expression of hasA with other has genes enhances HA yield and molecular weight ( Chauhan et al, 2014 , Prasad et al, 2010 , Widner et al, 2005 , Yu and Stephanopoulos, 2008 ). In L. lactis , it was shown that combination of three genes ( hasABC and hasABD ) was the optimum for higher HA yield ( Chauhan et al, 2014 , Prasad et al, 2010 , Prasad et al, 2012 ).…”

“…Earlier studies have correlated lower HA yield with excessive lactate production in L . lactis cultures ( Chauhan et al, 2014 ). In the present study, a three-fold increase was observed in the amount as well as molecular weight of HA produced by recombinant ldh -mutant L .…”

Uncovering Novel Pathways for Enhancing Hyaluronan Synthesis in Recombinant Lactococcus lactis: Genome-Scale Metabolic Modeling and Experimental Validation

“…Some of these strategies have been experimentally observed to be effective in previous studies. For example, the traditional has operon genes have been cloned in various combinations in L. lactis to increase HA production [9,19,21]. Apart from the operon, other pathway genes like phosphoglucomutase have been over-expressed [43].…”

“…Accordingly, recombinant L. lactis strains producing HA were previously developed by our group [18,19]. These have been investigated to identify metabolic factors that affect HA yield [20][21][22][23]. However, until now, the entire canvas for metabolic modifications has only included the traditional carbon-backbone based pathway ( Figure 2).…”