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

Author:

Sheng Juzheng1,Ling Peixue2,Wang Fengshan13

Affiliation:

1. grid.27255.37 0000000417611174 Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences Shandong University 250012 Jinan China

2. grid.495839.a Shandong Academy of Pharmaceutical Science 250101 Jinan China

3. grid.27255.37 0000000417611174 National Glycoengineering Research Center Shandong University 250012 Jinan China

Abstract

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.

Publisher

Oxford University Press (OUP)

Subject

Applied Microbiology and Biotechnology,Biotechnology,Bioengineering

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