Invention Grant
- Patent Title: Method of constructing a recombinant Bacillus subtilis that can produce specific-molecular-weight hyaluronic acids
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Application No.: US15011509Application Date: 2016-01-30
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Publication No.: US09771607B2Publication Date: 2017-09-26
- Inventor: Jian Chen , Zhen Kang , Guocheng Du , Peng Jin
- Applicant: Jian Chen , Zhen Kang , Guocheng Du , Peng Jin
- Applicant Address: CN Wuxi, JS
- Assignee: Jiangnan University
- Current Assignee: Jiangnan University
- Current Assignee Address: CN Wuxi, JS
- Agent Lili Chen
- Priority: CN201510573851 20150910
- Main IPC: C07K14/00
- IPC: C07K14/00 ; C12P19/26 ; C12N9/26 ; C12N9/04 ; C12N9/12 ; C12N9/90 ; C12N9/10

Abstract:
The present invention relates to the field of biotechnology engineering. It provides a method of constructing a recombinant Bacillus subtilis that can produce specific-molecular-weight hyaluronic acids. By integranted expression of hasA from Streptococcus zooepidemicus and overexpression of genes of HA synthetic pathway, tuaD, glmU and glmS, high yield HA production was achieved in the recombinant strain. Additionally, introduction and functional expression of the leech hyaluronidase in the recombinant strain substantially increased the yield of HA to 19.38 g·L−1. Moreover, HAs with a broad range of molecular weights (103 Da to 106 MDa) were efficiently produced by controlling the expression level of hyaluronidase using RBS mutants with different translational strengths. The method of the present invention can be used to produce low molecular weight HAs at large scale in industrial applications.
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