Hyaluronic acid (HA) production through fermentation using GRAS strains has become a research hotspot. This study aimed to improve the HA yield of a GRAS HA-producing strain, Bacillus velezensis Z1, by UV mutagenesis and fermentation process optimization. After UV mutagenesis, mutant strain ZV1 was obtained with high HA yield, good stability, and negative hyaluronidase. Based on the single factor experiment, the fermentation medium composition was optimized with the Box-Behnken design and response surface analysis. The data indicated that the optimal medium compositions were glucose 69.5 g/L, tryptone 10.2 g/L, beef extract 14.8 g/L, and MgSO4·7H2 O 1.5 g/L. The fermentation conditions were further optimized by single factor experiment and orthogonal test design, and the optimal fermentation conditions were as follows: pH 7.0, shaking speed 150 r/min, temperature 35 ℃, medium volume 140 mL. Under the optimal medium and fermentation conditions, the maximum HA yield of the mutant strain ZV1 reached 1.169 g/L, which was increased by 51.03% compared with that of the original strain Z1. Therefore, the HA yield of Bacillus velezensis Z1 was effectively improved by UV mutagenesis and optimization of fermentation process, which has a certain application value for the production of HA by industrial fermentation.
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