scholarly journals Hyaluronic Acid Production in Bacillus subtilis

2005 ◽  
Vol 71 (7) ◽  
pp. 3747-3752 ◽  
Author(s):  
Bill Widner ◽  
Régine Behr ◽  
Steve Von Dollen ◽  
Maria Tang ◽  
Tia Heu ◽  
...  

ABSTRACT The hasA gene from Streptococcus equisimilis, which encodes the enzyme hyaluronan synthase, has been expressed in Bacillus subtilis, resulting in the production of hyaluronic acid (HA) in the 1-MDa range. Artificial operons were assembled and tested, all of which contain the hasA gene along with one or more genes encoding enzymes involved in the synthesis of the UDP-precursor sugars that are required for HA synthesis. It was determined that the production of UDP-glucuronic acid is limiting in B. subtilis and that overexpressing the hasA gene along with the endogenous tuaD gene is sufficient for high-level production of HA. In addition, the B. subtilis-derived material was shown to be secreted and of high quality, comparable to commercially available sources of HA.

2021 ◽  
Vol 9 (2) ◽  
pp. 312
Author(s):  
João Heitor Colombelli Manfrão-Netto ◽  
Enzo Bento Queiroz ◽  
Kelly Assis Rodrigues ◽  
Cintia M. Coelho ◽  
Hugo Costa Paes ◽  
...  

Hyaluronic acid (HA) is a biopolymer formed by UDP-glucuronic acid and UDP-N-acetyl-glucosamine disaccharide units linked by β-1,4 and β-1,3 glycosidic bonds. It is widely employed in medical and cosmetic procedures. HA is synthesized by hyaluronan synthase (HAS), which catalyzes the precursors’ ligation in the cytosol, elongates the polymer chain, and exports it to the extracellular space. Here, we engineer Ogataea (Hansenula) polymorpha for HA production by inserting the genes encoding UDP-glucose 6-dehydrogenase, for UDP-glucuronic acid production, and HAS. Two microbial HAS, from Streptococcus zooepidemicus (hasAs) and Pasteurella multocida (hasAp), were evaluated separately. Additionally, we assessed a genetic switch using integrases in O. polymorpha to uncouple HA production from growth. Four strains were constructed containing both has genes under the control of different promoters. In the strain containing the genetic switch, HA production was verified by a capsule-like layer around the cells by scanning electron microscopy in the first 24 h of cultivation. For the other strains, the HA was quantified only after 48 h and in an optimized medium, indicating that HA production in O. polymorpha is limited by cultivation conditions. Nevertheless, these results provide a proof-of-principle that O. polymorpha is a suitable host for HA production.


2014 ◽  
Vol 950 ◽  
pp. 13-17 ◽  
Author(s):  
Xiao Fang ◽  
Rong Shuai Duan ◽  
Hai Ying Yang ◽  
Jing Feng Liu

Hyaluronic acid is an important polysaccharide of various physiological functions. Nowadays, it is produced mainly through microbial fermentation of Streptococcus zooepidemicus. HA production in more safe and efficient genetic modified GRAS strains is a hot research area. Bacillus subtilis, Lactococcus lactis, Streptococcus thermophiles, Agrobacterium sp. , and some Escherichia coli strains, which were GRAS strains, had been selected for genetic engineering to express hyaluronic acid. Here, we provide a comprehensive review of HA production by these genetic modified GRAS strains.


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