Skip to main content
Log in

Low cost and sustainable hyaluronic acid production in a manufacturing platform based on Bacillus subtilis 3NA strain

  • Biotechnological products and process engineering
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

A Correction to this article was published on 23 August 2021

This article has been updated

Abstract

Hyaluronic acid (HA) is a high value glycosaminoglycan mostly used in health and cosmetic applications. Commercial HA is produced from animal tissues or in toxigenic bacteria of the genus Streptococcus grown in complex media, which are expensive and raise environmental concerns due to the disposal of large amounts of broth with high organic loads. Other microorganisms were proposed as hosts for the heterologous production of HA, but the methods are still costly. The extraordinary capacity of this biopolymer to bind and retain water attracts interest for large-scale applications where biodegradable materials are needed, but its high cost and safety concerns are barriers for its adoption. Bacillus subtilis 3NA strain is prototrophic, amenable for genetic manipulation, GRAS, and can rapidly reach high cell densities in salt-based media. These phenotypic traits were exploited to create a platform for biomolecule production using HA as a proof of concept. First, the 3NA strain was engineered to produce HA; second, a chemically defined medium was formulated using commodity-priced inorganic salts combined at the stoichiometric ratios needed to build the necessary quantities of biomass and HA; and third, a scalable fermentation process, where HA can be produced at the maximum volumetric productivity (VP), was designed. A comparative economic analysis against other methods indicates that the new process may increase the operating profit of a manufacturing plant by more than 100%. The host, the culture medium, and the rationale employed to develop the fermentation process described here, introduce an IP-free platform that could be adaptable for production of other biomolecules.

Key points

• A biomolecule production platform based on B. subtilis 3NA strain and a synthetic medium was tested for hyaluronic acid biosynthesis

• A fermentation process with the maximum volumetric productivity was designed

• A techno-economic analysis forecasts a significant reduction in the manufacturing cost compared to the current methods

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Change history

References

Download references

Acknowledgements

The authors want to acknowledge Juan Diego All, Mauro Nicolás Cerchi, and Claudio Exequiel Cansino Quispe for their technical assistance.

Funding

Part of this work was supported by Glyco@Alps (ANR-15-IDEX-02).

Author information

Authors and Affiliations

Authors

Contributions

SC, HM, and BP conceived and designed research. SC, ML, SP, and PA conducted experiments. BP and JCA contributed new reagents or analytical tools. SC and HM analyzed data. SC and HM wrote the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Sebastián Cerminati.

Ethics declarations

Ethics approval

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

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(PDF 1018 kb)

ESM 2

(XLSX 51 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cerminati, S., Leroux, M., Anselmi, P. et al. Low cost and sustainable hyaluronic acid production in a manufacturing platform based on Bacillus subtilis 3NA strain. Appl Microbiol Biotechnol 105, 3075–3086 (2021). https://doi.org/10.1007/s00253-021-11246-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-021-11246-6

Keywords

Navigation