Hyaluronic acid is a glycosaminoglycan widely used in medicine, cosmetics and food industries. The main industrial production strain of hyaluronic acid is Streptococcus zooepidemicus. Because the bacteria are pathogenic, there is an urgent need to construct a safe hyaluronic acid producing strain. By heterologous expression of hyaluronic acid synthase (pmHasA) in a food-grade expression host, Corynebacterium glutamicum, the synthesis of current hyaluronic acid was achieved, and the yield in shake flasks reached 0.35 g/L. By enhancing the expression of the UDP-glucose dehydrogenase gene (ugdA2) and phosphoaminotransferase gene (glmS) in the metabolic pathway and knocking out the lactate dehydrogenase gene (ldh), the yield of hyaluronic acid increased to 0.81 g/L. Based on this, the induction conditions were optimized, and the optimal isopropyl-β-D-thiogalactopyranoside (IPTG) concentration was determined to be 0.8 mmol/L, and the induction time was 2 hours. Under these conditions, the highest yield of hyaluronic acid in shake flask was 1 g/L. After batch fed fermentation in a 3 L fermenter, the hyaluronic acid yield reached 4.8 g/L. In this paper, the safe and efficient synthesis of hyaluronic acid was achieved by regulating the metabolic pathway of Corynebacterium glutamicum, which laid the foundation for the production of food-grade hyaluronic acid.
HU Litao
,
WANG Yang
,
LI Jialian
,
ZHOU Siyan
,
WANG Daoan
,
YIN Guobin
,
LIU Jingjing
,
KANG Zhen
,
CHEN Jian
. Metabolic engineering of Corynebacterium glutamicum for hyaluronic acid production[J]. Food and Fermentation Industries, 2020
, 46(18)
: 1
-7
.
DOI: 10.13995/j.cnki.11-1802/ts.023858
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