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A kind of recombinant microorganism producing sialic acid and its application

A technology for recombinant microorganisms and sialic acid, applied in microorganisms, microorganism-based methods, recombinant DNA technology, etc., can solve the problems of low yield of sialic acid and difficult to meet industrial production, and achieve lower production costs, efficient transformation, and important industrial applications. effect of value

Active Publication Date: 2022-06-17
TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the yield of sialic acid produced by the existing fermentation method is still very low, which is difficult to meet the needs of industrial production

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0075] The construction of the starting strain of embodiment 1

[0076] In this example, taking Escherichia coli BL21 as an example, a starting strain capable of synthesizing sialic acid was constructed, specifically: knocking out the nanATEK gene cluster in Escherichia coli BL21 (purchased from China Industrial Microorganism Culture Collection Center), and introducing the overexpression plasmid pXMJ at the same time -neuBC, to obtain the starting strain BL21ΔnanATEK / pXMJ-neuBC capable of producing sialic acid.

[0077] 1. Knockout of nanATEK

[0078] 利用Red重组方法敲除nanATEK(基因簇序列如SEQ ID NO.16所示),具体方法如下:以nan-F(ggtataacaggtataaaggtatatcgtttatcagacaagcatcacttcagaggtatttgtgtaggctggagctgcttc)和nan-R(tcataatttttctccctgggccaacagcgcagccccaagtaaacctgcatcatggcggtaatgcgccgccctgtcaaacatgagaattaa)为引物,以质粒pKD13(购自Addgene) A 1.3Kb PCR fragment was obtained for template amplification, which was transferred into E. coli BL21 containing plasmid pSIJ8 (purchased from Addgene) by electroporation, and ...

Embodiment 2

[0083] Example 2 Construction of recombinant bacteria overexpressing glucosamine 6-phosphate synthase or its mutant

[0084] On the basis of the starting strain constructed in Example 1, further overexpress glucosamine 6-phosphate synthase (the amino acid sequence is shown in SEQ ID NO.1, and the coding gene sequence is shown in SEQ ID NO.2) or its mutant E15K+D387V+S450P+E525G (the amino acid sequence is shown in SEQ ID NO.11, and the coding gene sequence is shown in SEQ ID NO.12), the specific method is as follows:

[0085] 1. Construction of a plasmid overexpressing glucosamine-6-phosphate synthase glmS or its mutant glmS*

[0086] Artificially synthesized glmS* mutant gene, the sequence is shown in SEQ ID NO.12, the sequence contains the following mutation E15K compared with glmS (wild-type glmS, sequence shown in SEQ ID NO.2) derived from Escherichia coli W3110, D387V, S450P, E525G, the enzyme activity is higher and not inhibited by acetylglucosamine compared with wild-t...

Embodiment 3

[0089] Example 3 Construction of recombinant bacteria overexpressing glucosamine 6-phosphate synthase and fructose-1,6-bisphosphatase simultaneously

[0090] Fructose-1,6-bisphosphatase can catalyze the dephosphorylation of fructose-1,6-bisphosphate to produce fructose 6-phosphate. The present invention finds that on the basis of overexpressing glucosamine 6-phosphate synthase or its mutant, further Overexpression of fructose-1,6-bisphosphatase glpX could further increase the production of sialic acid.

[0091] Simultaneously overexpress Escherichia coli 6-phosphate glucosamine synthase (the amino acid sequence is shown in SEQ ID NO.1, the coding gene sequence is shown in SEQ ID NO.2) or its mutant (the amino acid sequence is shown in SEQ ID NO.11) shown, the coding gene sequence is shown in SEQ ID NO.12) and fructose-1,6-bisphosphatase (the amino acid sequence is shown in SEQ ID NO.3, the coding gene sequence is shown in SEQ ID NO.4) The construction method of recombinant ba...

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Abstract

The invention relates to the technical field of microbial fermentation, in particular to a recombinant microorganism producing sialic acid and its application. The present invention provides a recombinant microorganism having increased expression of glucosamine-6-phosphate synthetase or a mutant thereof, and increased fructose-1,6-bisphosphatase compared to a starting strain capable of synthesizing sialic acid and / or expression of glutamine synthetase. The present invention obtains the recombinant microorganism capable of fermenting and producing sialic acid from cheap carbon sources such as glucose and glycerin by transforming the microorganism, and the production of sialic acid of the recombinant microorganism has been significantly improved, realizing the production of sialic acid from cheap carbon sources such as glucose and glycerol. The efficient conversion to sialic acid significantly reduces the production cost of sialic acid and has important industrial application value.

Description

technical field [0001] The invention relates to the technical field of microbial fermentation, in particular to a sialic acid-producing recombinant microorganism and its application. Background technique [0002] Sialic acid, also known as N-acetylneuraminic acid, is an important physiologically active substance in the human body, and is the main component of brain gangliosides and glycoproteins. Sialic acid is the most important functional component in traditional Chinese rare food bird's nest, and it is also one of the components in colostrum that plays an important role in the development of the infant's early brain and the improvement of the immune system. Studies have found that sialic acid is an indispensable nutrient for brain development. Sialic acid is closely related to the normal development of infant brain. Supplementing sialic acid is beneficial to the formation of human learning and memory. At present, sialic acid has been widely used in infant formula food, h...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N1/21C12N15/70C12N15/77C12P19/26C12R1/19C12R1/15
CPCC12N9/00C12N9/16C12N15/77C12N15/70C12P19/26
Inventor 陈振刘德华
Owner TSINGHUA UNIV