Exploiting the diversity of streptococcal hyaluronan synthases for the production of molecular weight–tailored hyaluronan
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The molecular weight (Mw) of hyaluronic acid (HA) determines its suitability for medical and cosmetic applications. Here, we characterize in vitro and in vivo HA synthesis of streptococcal HA synthases (HASs) with a special focus on HA Mw. To date, four streptococcal HA producers are described (Streptococcus equi subsp. equi, S. equi subsp. zooepidemicus, S. pyogenes, and S. uberis). We identified two more potential HA producers in this study: S. iniae and S. parauberis. Indeed, the HA Mw produced by the different streptococcal HASs differs in vitro. To exploit these different HA Mw synthesis capacities, Lactococcus lactis strains expressing the streptococcal HASs were constructed. HA of different Mw was also produced in vivo by these engineered strains, strongly suggesting that the protein sequences of the HASs influence HA Mw. Since the HA Mw in vivo is also influenced by metabolic factors like specific growth rate and HA precursor availability, these were also determined. In summary, the maximal Mw of HA synthesized is specific for the individual synthase, while any decrease from the maximal HA Mw is influenced by physiological and metabolic factors. The results open new avenues for Mw-tailored HA synthesis.
KeywordsHyaluronic acid Molecular weight Streptococci Hyaluronic acid synthase Specific growth rate Intracellular precursor availability Molecular weight control
The authors would like to thank Prof. Lars K. Nielsen from the University of Queensland for providing strain S. zooepidemicus ATCC 35246 and Dr. Mark van der Linden from the National Reference Laboratory (NRZ) on streptococcal diseases for providing genomic DNA of four streptococci. Moreover, the authors kindly thank John Mandawe from the Institute of Biotechnology, RWTH Aachen University, for helpful discussions about in vitro HA synthesis assays.
This study was partly funded by the German Federal Environmental Foundation (grant number AZ 30812-32) and by the German Federal Ministry of Education and Research (grant number 031B0104A). Moreover, the study was financially supported by the Strategic Partnership RWTH Aachen and IIT Madras through a travel grant.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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