Constructing a recombinant hyaluronic acid biosynthesis operon and producing food-grade hyaluronic acid in Lactococcus lactis

Abstract

Hyaluronic acid (HA), a natural high molecular weight polysaccharide, is produced by Streptococcus zooepidemicus. However, Streptococcus has several drawbacks including its potential to produce exotoxins, so there is demand for an alternative HA source. Here, a recombinant HA biosynthesis operon, as well as the HA biosynthesis operon of S. zooepidemicus were introduced into L. lactis using the nisin-controlled expression system, respectively. HA was successfully synthesized by recombinant L. lactis. Furthermore, overexpression of the endogenous enzymes directing the synthesis of precursor sugars was effective at increasing HA production, and increasing the supply of UDP-activated monosaccharide donors aided synthesis of monodisperse HA polysaccharides. Besides GRAS host strain (L. lactis) and NICE system, the selecting marker (lacF gene) of the recombinant strain is also food grade. Therefore, HA produced by recombinant L. lactis overcomes the problems associated with Streptococcus and provides a source of food-grading HA appropriate for widespread biotechnological applications.

Homologous Overexpression of Genes in Cordyceps militaris Improves the Production of Polysaccharide

“…The GlcA, which plays an important role in the uronic acid pathway and hyaluronic acid synthesis [29,30].…”

Microbial production of value-added nutraceuticals

“…Bacterial polysaccharides such as xanthan, gellan, dextrans and alginate can be commercialized via microbial production and purification [40]. [42][43][44]. Medicinally important polysaccharides such as heparosan and chondroitin can be produced by engineered E. coli reaching a relatively high titer of 1.88 g/L and 2.4 g/L, respectively (Table 1) [45,46].…”

The effect of hyaluronic acid addition on the properties of smoked homogenised sausages

“…This, in turn, poses a risk of contamination of the hyaluronate with bacterial exotoxins and prevents its use in food products. In order to avoid the contamination of bacterial produced HA, some researchers developed bacterial strains that are able to produce hyaluronate and are labelled as GRAS (Generally Recognised As Safe), such as Lactobacillus lactis or Corynebacterium glutamicum …”

“…In order to avoid the contamination of bacterial produced HA, some researchers developed bacterial strains that are able to produce hyaluronate and are labelled as GRAS (Generally Recognised As Safe), such as Lactobacillus lactis or Corynebacterium glutamicum. 7,8 One of the main properties of HA is its highly hydrophilic nature, which allows it to trap approximately 1000 times its weight in water, 9 by forming a special coil structure, 10 which makes it an ideal lubricant. 4 Currently, hyaluronic acid is broadly used in medicine, as treatment in various medical conditions such as osteoarthritis, 11,12 dry eye, 13 otosclerosis surgery, 14 non-reducing disc displacement, 15 tissue engineering 16 or even drug delivery agent.…”