Applied Microbiology and Biotechnology

, Volume 103, Issue 18, pp 7567–7581 | Cite as

Exploiting the diversity of streptococcal hyaluronan synthases for the production of molecular weight–tailored hyaluronan

  • Sandra Schulte
  • Sreeja Shanmuga Doss
  • Pandeeswari Jeeva
  • Mythili Ananth
  • Lars M. BlankEmail author
  • Guhan JayaramanEmail author
Biotechnologically relevant enzymes and proteins


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.


Hyaluronic 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.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

253_2019_10023_MOESM1_ESM.pdf (248 kb)
ESM 1 (PDF 247 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.iAMB – Institute of Applied Microbiology, ABBt – Aachen Biology and BiotechnologyRWTH Aachen UniversityAachenGermany
  2. 2.Department of Biotechnology, Bhupat and Jyoti Mehta School of BiosciencesIndian Institute of Technology MadrasChennaiIndia
  3. 3.Department of Chemical EngineeringIndian Institute of Technology MadrasChennaiIndia
  4. 4.BioSC, c/o Forschungszentrum JülichJülichGermany

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