Heterologous Biosynthesis of Hyaluronic Acid Using a New Hyaluronic Acid Synthase Derived from the Probiotic <i>Streptococcus thermophilus</i>
Hyaluronic acid (HA) is a natural linear polysaccharide extensively used in many fields, including the food, medicine, and cosmetics industries. Currently, species that produce HA synthetase (HAS) from microbial sources are relatively small and mainly pathogenic, such as <i>Streptococcus pyoge...
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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | Fermentation |
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| Online Access: | https://www.mdpi.com/2311-5637/9/6/510 |
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| author | Qian Zhong Yanqin Ma Delei Xu Peng Lei Sha Li Hong Xu Yibin Qiu |
| author_facet | Qian Zhong Yanqin Ma Delei Xu Peng Lei Sha Li Hong Xu Yibin Qiu |
| author_sort | Qian Zhong |
| collection | DOAJ |
| description | Hyaluronic acid (HA) is a natural linear polysaccharide extensively used in many fields, including the food, medicine, and cosmetics industries. Currently, species that produce HA synthetase (HAS) from microbial sources are relatively small and mainly pathogenic, such as <i>Streptococcus pyogenes</i> and <i>Pasteurella multicide</i>. Moreover, there is limited research on the safe microbial sources of HAS. Thus, we characterized SthasA, a HAS derived from the probiotic <i>Streptococcus thermophilus</i>, and used it for the de novo synthesis of HA in a chassis strain of <i>Bacillus amyloliquefaciens</i>. Metabolic engineering of the precursor supply modules suggested that <i>hasB</i> (encoding UDPG dehydrogenase), which was derived from <i>Corynebacterium glutamicum</i> ATCC 13032, effectively promoted the accumulation of HA products. Furthermore, by combining the expression of the global regulatory factor CcpA, HA yield from the recombinant strain reached 3.20 g/L. Finally, we obtained a yield of 5.57 g/L HA with a molecular weight of 1.7 × 10<sup>6</sup> Da using various process optimization strategies in a 5 L bioreactor. This study enriches our understanding of obtaining HAS from non-pathogenic bacteria and provides a safe and effective process for producing HA, which has the potential to promote the industrial applications of HA further. |
| first_indexed | 2024-03-11T02:29:53Z |
| format | Article |
| id | doaj.art-96b392d0bdc24b92b988043f781750e6 |
| institution | Directory Open Access Journal |
| issn | 2311-5637 |
| language | English |
| last_indexed | 2024-03-11T02:29:53Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Fermentation |
| spelling | doaj.art-96b392d0bdc24b92b988043f781750e62023-11-18T10:20:45ZengMDPI AGFermentation2311-56372023-05-019651010.3390/fermentation9060510Heterologous Biosynthesis of Hyaluronic Acid Using a New Hyaluronic Acid Synthase Derived from the Probiotic <i>Streptococcus thermophilus</i>Qian Zhong0Yanqin Ma1Delei Xu2Peng Lei3Sha Li4Hong Xu5Yibin Qiu6State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250353, ChinaState Key Laboratory of Materials-Oriented Chemical Engineering, College of Food Science and Light Industry, Nanjing Tech University, Nanjing 211816, ChinaCollege of Biological and Food Engineering, Changshu Institute of Technology, Changshu 215500, ChinaState Key Laboratory of Materials-Oriented Chemical Engineering, College of Food Science and Light Industry, Nanjing Tech University, Nanjing 211816, ChinaState Key Laboratory of Materials-Oriented Chemical Engineering, College of Food Science and Light Industry, Nanjing Tech University, Nanjing 211816, ChinaState Key Laboratory of Materials-Oriented Chemical Engineering, College of Food Science and Light Industry, Nanjing Tech University, Nanjing 211816, ChinaState Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250353, ChinaHyaluronic acid (HA) is a natural linear polysaccharide extensively used in many fields, including the food, medicine, and cosmetics industries. Currently, species that produce HA synthetase (HAS) from microbial sources are relatively small and mainly pathogenic, such as <i>Streptococcus pyogenes</i> and <i>Pasteurella multicide</i>. Moreover, there is limited research on the safe microbial sources of HAS. Thus, we characterized SthasA, a HAS derived from the probiotic <i>Streptococcus thermophilus</i>, and used it for the de novo synthesis of HA in a chassis strain of <i>Bacillus amyloliquefaciens</i>. Metabolic engineering of the precursor supply modules suggested that <i>hasB</i> (encoding UDPG dehydrogenase), which was derived from <i>Corynebacterium glutamicum</i> ATCC 13032, effectively promoted the accumulation of HA products. Furthermore, by combining the expression of the global regulatory factor CcpA, HA yield from the recombinant strain reached 3.20 g/L. Finally, we obtained a yield of 5.57 g/L HA with a molecular weight of 1.7 × 10<sup>6</sup> Da using various process optimization strategies in a 5 L bioreactor. This study enriches our understanding of obtaining HAS from non-pathogenic bacteria and provides a safe and effective process for producing HA, which has the potential to promote the industrial applications of HA further.https://www.mdpi.com/2311-5637/9/6/510hyaluronic acidcell factoryhyaluronic acid synthetase<i>Streptococcus thermophilus</i>synthetic biology |
| spellingShingle | Qian Zhong Yanqin Ma Delei Xu Peng Lei Sha Li Hong Xu Yibin Qiu Heterologous Biosynthesis of Hyaluronic Acid Using a New Hyaluronic Acid Synthase Derived from the Probiotic <i>Streptococcus thermophilus</i> Fermentation hyaluronic acid cell factory hyaluronic acid synthetase <i>Streptococcus thermophilus</i> synthetic biology |
| title | Heterologous Biosynthesis of Hyaluronic Acid Using a New Hyaluronic Acid Synthase Derived from the Probiotic <i>Streptococcus thermophilus</i> |
| title_full | Heterologous Biosynthesis of Hyaluronic Acid Using a New Hyaluronic Acid Synthase Derived from the Probiotic <i>Streptococcus thermophilus</i> |
| title_fullStr | Heterologous Biosynthesis of Hyaluronic Acid Using a New Hyaluronic Acid Synthase Derived from the Probiotic <i>Streptococcus thermophilus</i> |
| title_full_unstemmed | Heterologous Biosynthesis of Hyaluronic Acid Using a New Hyaluronic Acid Synthase Derived from the Probiotic <i>Streptococcus thermophilus</i> |
| title_short | Heterologous Biosynthesis of Hyaluronic Acid Using a New Hyaluronic Acid Synthase Derived from the Probiotic <i>Streptococcus thermophilus</i> |
| title_sort | heterologous biosynthesis of hyaluronic acid using a new hyaluronic acid synthase derived from the probiotic i streptococcus thermophilus i |
| topic | hyaluronic acid cell factory hyaluronic acid synthetase <i>Streptococcus thermophilus</i> synthetic biology |
| url | https://www.mdpi.com/2311-5637/9/6/510 |
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