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Efficient production of high-molecular-weight hyaluronic acid with a two-stage fermentation
J. Liu,Y. Wang,Z. Li,Y. Ren,Y. Zhao,G. Zhao
RSC Advances Pub Date : 10/24/2018 00:00:00 , DOI:10.1039/C8RA07349J
Abstract

In this paper, the production pattern of hyaluronic acid (HA) was revealed: the chain growth of HA mainly occurred in the first half of fermentation while the product accumulated throughout the fermentation period. Attempts were made to develop a two-stage fermentation process which provided high-level synthesis in both product titer and molecular weight. The pH was kept at 8.0 with a temperature of 31 °C in the first fermentation stage (0–10 h) to promote the growth of weight-average molecular weight (Mw), and the pH and temperature were maintained at 7.0 and 37 °C, respectively, in the following fermentation stage to facilitate HA accumulation. In addition, constant rates of aeration (1 vvm) and agitation (600 rpm) were adopted. The two-stage fermentation provided a balanced result in which a product titer of 4.75 g L−1 and a Mw of 2.36 × 106 Da were achieved under optimized conditions. The process introduces an effective way to produce HA considering the effect of segmented control strategy.

Graphical abstract: Efficient production of high-molecular-weight hyaluronic acid with a two-stage fermentation
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