ArticleMolecular biotechnology2014
The role of hyaluronic acid precursor concentrations in molecular weight control in Streptococcus zooepidemicus.
Article in Molecular biotechnology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 39 citations in OpenAlex.
- Comparative evaluation of glucosamine derivatives for enhanced microbial hyaluronic acid production by Streptococcus zooepidemicus and Streptococcus pyogenes.Archives of microbiology · 2026Article
- Tailored molecular weight hyaluronic acid production by engineered Lactococcus lactis.Microbial cell factories · 2026Article
- Molecular weight regulation strategies in microbial synthesis of hyaluronic acid: current status and future perspectives.World journal of microbiology & biotechnology · 2025Review
- Inducible engineering precursor metabolic flux for synthesizing hyaluronic acid of customized molecular weight in Streptococcus zooepidemicus.Microbial cell factories · 2025Article
- Article
- Mechanobiology of Hyaluronan: Connecting Biomechanics and Bioactivity in Musculoskeletal Tissues.Annual review of biomedical engineering · 2024Review
- Prospective bacterial and fungal sources of hyaluronic acid: A review.Computational and structural biotechnology journal · 2022Review
- Collagen- and hyaluronic acid-based hydrogels and their biomedical applications.Materials science & engineering. R, Reports : a review journal · 2021Article
- Production and purification of higher molecular weight chondroitin by metabolically engineered Escherichia coli K4 strains.Scientific reports · 2020Article
- Deciphering the role of dissolved oxygen and N-acetyl glucosamine in governing higher molecular weight hyaluronic acid synthesis in Streptococcus zooepidemicus cell factory.Applied microbiology and biotechnology · 2020Article
- Efficient production of high-molecular-weight hyaluronic acid with a two-stage fermentation.RSC advances · 2018Article
- Construction of efficient Streptococcus zooepidemicus strains for hyaluoronic acid production based on identification of key genes involved in sucrose metabolism.AMB Express · 2016Article
- Replenishing the cyclic-di-AMP pool: regulation of diadenylate cyclase activity in bacteria.Current genetics · 2016Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The biosynthetic pathway responsible for the production of hyaluronic acid (HA) has been thoroughly studied; however, many aspects remain elusive regarding the mechanisms that control molecular weight (MW). Previously, we demonstrated a positive correlation between MW and the concentration of the HA precursor sugar UDP-N acetylglucosamine (UDP-GlcNAc). To further investigate the role of UDP-GlcNAc in MW control, we increased the intracellular concentration of this monomer using both feeding strategies and genetic engineering approaches. Feeding cells glucosamine dramatically increased intracellular levels of UDP-GlcNAc, but unexpectedly, produced HA of a lower MW. This was subsequently attributed to an equally dramatic decrease in the level of the other HA precursor sugar UDP-glucuronic acid (UDP-GlcUA). Feeding cells a mixture of glucose and GlcNAc addressed this imbalance of precursor sugars, leading to an increase in both UDP-GlcNAc and UDP-GlcUA; however, no significant increase in MW was observed. Despite the increase in UDP-sugars, RNA sequencing identified no increase in the expression of the genes involved in production of HA. Returning to genetic engineering approaches to examine UDP-GlcNAc and MW, genes known to contribute to the production of UDP-GlcNAc were over-expressed, both individually and together. Using this approach, UDP-GlcNAc and MW increased. At lower levels of UDP-GlcNAc, the positive correlation between UDP-GlcNAc levels and MW was maintained, however this relationship stalled at higher concentrations of UDP-GlcNAc. Taken together, these results suggest that while optimising HA precursor levels using feeding or genetic engineering approaches can improve HA MW, there is a point at which excess availability of precursors is no longer advantageous. Once precursor concentrations are addressed, it would seem that other uncharacterised factor(s) (e.g. rate of HA synthesis) also contribute to HA MW control.
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