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

Abstract

A two-stage fermentation process with a segmented control strategy provides high-level synthesis in both HA titer and molecular weight.

Comprehensive review on biotechnological production of hyaluronic acid: status, innovation, market and applications

“…The initial-stage fermentation was maintained at 31°C with pH 8.0 for enhancing the MW of HA, and during the accumulation stage, the temperature and pH were held at 37°C and 7.0, respectively. The proposed two-stage fermentation resulted in an optimized result with high titers of HA [ 43 ] .…”

A Review on Current Strategies for Extraction and Purification of Hyaluronic Acid

“…On the other hand, a moderate agitation of 600 nm demonstrated the improvement of HA yield, concluding that pH, aeration, temperature, and agitation parameters have to be controlled in order to obtain the best results. In this case, Liu et al obtained a yield of 4.75 g/L of HA with a molecular weight of 2360 kDa [ 33 ]. This work highlights the importance of fermentation parameters as a way to obtain HA with desired characteristics, either high or low molecular weight or simply to increase product yield.…”

Prospective bacterial and fungal sources of hyaluronic acid: A review

“…In industry, HA is obtained mainly by biological methods such as extraction from animal sources with application of cetylpyridinium chloride precipitation [12] or microbial fermentation [13] . Besides that, a wide range of synthetic approaches are available nowadays, such as chemical, chemoenzymatic and enzymatic methods.…”

“…: fermentation conditions, yield and molecular weight. Strain Fermentation conditions HA yield (g/l) HA MW (×10 6 Da) Reference S. zooepidemicus ATCC 39,920 Medium : 50 g/l sucrose; 3,5 g/l yeast extract; 10 g/l casein enzyme hydrolysate; 2 g/l K 2 HPO 4 ; 1.5 g/l NaCl; 0.4 g/l MgSO 4 ·7H 2 O Aeration : 2 vvm Temperature : 37 °C Duration : 28 h pH : 7 Impeller speed : 400 rpm 5.00 3.50–3.90 [175] S. zooepidemicus 3523 Medium : 50 g/l glucose; 10 g/l yeast extract; 3 g/l MgSO 4 ·7H 2 O; 1.5 g/l K 2 HPO 4 ; 3 g/l KH 2 PO 4 ; 5 g/l NH 4 Cl Aeration : ND Temperature : 37 °C Duration : 12–14 h pH : 7 Impeller speed : 400 rpm 2.80 1.59 [242] S. zooepidemicus HA-13–06 Medium : 70 g/l glucose; 10 g/l yeast extract; 5 g/l tryptone; 0.4 g/l MgSO 4 ·7H 2 O; 1.8 g/l K 2 HPO 4 Aeration : 1 vvm Temperature : from 31 °C to 37 °C Duration : 24 h pH : from 8.0 to 7.0 Impeller speed : 250 rpm 4.75 2.36 [12] S. zooepidemicus MTCC 3523 Medium : 20.0 g/l palmyra palm jaggery; 2.5 g/l yeast extract; 2.5 g/l peptic digest of animal tissue; 2.5 g/l casein enzyme hydrolysate; 5.0 g/l peptic digest of soybean meal; 5 g/l beef extract; 0.5 g/l ascorbic acid; 0.25 g/l MgSO 4 ; 19.0 g/l disodium β glycerophosphate Aeration : 1 vvm Temperature : 37 °C Duration : overnight pH : 7 Impeller speed : 180 rpm 5.96 0.93–0.96 [243] S. zooepidemicus ATCC 39,920 Medium : 85.35 g/l sugarcane molasses, 50 g/l yeast extract; 2.5 g/l K 2 HPO 4 ; 2.0 g/l NaCl; 1.5 g/l MgSO 4 Aeration : 0.5 vvm Temperature : 37 °C Duration : 24 pH : 8 Impeller speed : 100 rpm …”

“…Extraction from animal sources has been considered a traditional method for obtaining hyaluronic acid for years, however it is not associated with large scale production anymore [12] . Currently, the most common industrial production process employed to obtain HA is streptococcal fermentation [13] .…”