Hyaluronic acid production enhancement via genetically modification and culture medium optimization in Lactobacillus acidophilus

Int J Biol Macromol. 2019 Jan:121:870-881. doi: 10.1016/j.ijbiomac.2018.10.112. Epub 2018 Oct 17.

Abstract

Hyaluronic acid (HA) is a natural polymer with various molecular weights that specify multiple biological roles. Traditionally, HA is obtained from animal waste and conventional pathogenic streptococci. However, there are challenges in these processes such as the presence of exotoxins, hyaluronidase, and viral contamination. In order to reduce these problems, this study was conducted to produce HA using recombinant bacterium that is generally recognized as safe (GRAS), and thereafter increase production through experimental design. At first, some lactic acid bacteria were screened and evaluated for HA production. Accordingly, among the selected bacteria, Lactobacillus acidophilus PTCC1643 produced about 0.25 g HA/L in the 48th hour of cultivation, and was thus selected as an alternative host for heterologous HA production. An expression vector containing HA synthase genes was transformed into L. acidophilus by electroporation. Consequently, HA production increased to 0.4 g/L. Eventually, response surface method (RSM) was used, which increased HA production to 1.7 g/L. This is approximately 7-fold higher than that produced at first. The resulting HA was characterized by FTIR spectroscopy and its molecular weight was estimated using agarose gel electrophoresis. In conclusion, L. acidophilus could be a safe, effective, and novel HA producer with industrial potential and commercial prospects.

Keywords: Electroporation; GRAS bacteria; Hyaluronic acid; Response surface methodology.

MeSH terms

  • Culture Media / chemistry*
  • Electroporation
  • Genetic Engineering*
  • Hyaluronic Acid / biosynthesis*
  • Hyaluronoglucosaminidase / genetics
  • Hyaluronoglucosaminidase / metabolism
  • Lactobacillus acidophilus / genetics*
  • Lactobacillus acidophilus / growth & development
  • Lactobacillus acidophilus / metabolism*
  • Molecular Weight

Substances

  • Culture Media
  • Hyaluronic Acid
  • Hyaluronoglucosaminidase