High-molecular-weight hyaluronic acid has biological functions of moisturizing and anti-inflammatory, and widely used in cosmetics and medical fields. In order to produce high-molecular-weight hyaluronic acid, the Pasteurella multocida pmhasA gene encoding hyaluronic acid synthase was expressed in Corynebacterium glutamicum. The molecular weight of hyaluronic acid was 1.51 MDa by optimized the codon and extraction method, 1.8 MDa by site-directed mutation a HA synthase variant (pmhasA T104A), and 3.3 MDa by strengthen the expression of UDP-glucose dehydrogenase gene (ugdA). On this basis, the highest molecular weight of hyaluronic acid in the shake flask reached to 4.8 MDa at 20 ℃. Finally, fed-batch fermentation was carried out in a 3 L fermenter, and the yield of high-molecular-weight hyaluronic acid reached 1.5 g/L. In conclusion, the safe and efficient synthesis of high-molecular-weight hyaluronic acid was achieved through synthase modification, metabolic pathway enhancement and culture condition optimization, which laid a foundation for the industrial production of high-molecular-weight hyaluronic acid.
WANG Hao
,
WANG Yang
,
HU Litao
,
KANG Zhen
,
DU Guocheng
. Production of high molecular weight hyaluronic acid by recombinant Corynebacterium glutamicum[J]. Food and Fermentation Industries, 2021
, 47(17)
: 15
-21
.
DOI: 10.13995/j.cnki.11-1802/ts.027184
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