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In vivo synthesis of sialylated compounds

A technology of sialylation and sialic acid synthase, which is applied in the fermentation of metabolic engineering microorganisms, synthetic biology and metabolic engineering, can solve the problems of high production cost, loss of productivity and titer, insufficient to meet the large demand of biotechnology, etc.

Pending Publication Date: 2019-08-09
因比奥斯公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition to loss of productivity and titer, another disadvantage of using an inducible system is the secretion of intermediate pathway metabolites such as GlcNAc and ManNAc
This results in additional downstream processing steps for purification and therefore higher production costs when producing sialic acid, sialyllactose or other sialylated compounds
[0014] The methods discussed above for the production of sialylated compounds are still insufficient to meet the high demands of the biotech, pharmaceutical and pharmaceutical industries

Method used

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  • In vivo synthesis of sialylated compounds
  • In vivo synthesis of sialylated compounds
  • In vivo synthesis of sialylated compounds

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Embodiment Construction

[0021] The present invention describes an economical, more efficient alternative biosynthetic pathway for the production of sialylated compounds using microorganisms.

[0022] The present invention provides methods for producing sialylated compounds by fermentative growth of microorganisms.

[0023] In particular, the invention relates to a method of producing a sialylated compound, wherein said method comprises culturing a microorganism in a culture medium. Microorganisms convert the following reactions intracellularly: N-acetylglucosamine-6-phosphate to N-acetylglucosamine, N-acetylglucosamine to N-acetylmannosamine, and N-acetylmannosamine It is N-acetylneuraminic acid. In addition, the microorganism is unable to: i) convert N-acetylglucosamine-6-P to glucosamine-6-P, ii) convert N-acetylglucosamine to N-acetylglucosamine-6-P , and iii) converting N-acetylneuraminic acid to N-acetylmannosamine.

[0024] Preferably, the conversion of N-acetylglucosamine-6-phosphate to N-a...

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Abstract

The present invention is in the technical field of synthetic biology and metabolic engineering. More particularly, the present invention is in the technical field of fermentation of metabolically engineered microorganisms. The present invention describes engineered microorganisms able to synthesize sialylated compounds via an intracellular biosynthesis route. These microorganisms can dephosphorylate N-acetylglucosamine-6-phosphate to N-acetylglucosamine and convert the N-acetylglucosamine to N-acetylmannosamine. These microorganisms also have the ability to convert N-acetylmannosamine to N-acetyl-neuraminate. Furthermore, the present invention provides a method for the large scale in vivo synthesis of sialylated compounds, by culturing a microorganism in a culture medium, optionally comprising an exogenous precursor such as, but not limited to lactose, lactoNbiose, N-acetyllactosamine and / or an aglycon, wherein said microorganism intracellularly dephosphorylates N-acetylglucosamine-6-phosphate to N-acetylglucosamine, converts N-acetylglucosamine to N- acetylmannosamine and convert the latter further to N-acetyl- neuraminate.

Description

technical field [0001] The invention belongs to the technical fields of synthetic biology and metabolic engineering. More specifically, the present invention belongs to the technical field of fermentation of metabolically engineered microorganisms. The present invention describes engineered microorganisms capable of synthesizing sialylated compounds via intracellular biosynthetic pathways. These microorganisms dephosphorylate N-acetylglucosamine-6-phosphate to N-acetylglucosamine and convert N-acetylglucosamine to N-acetylmannosamine. These microorganisms also convert N-acetylmannosamine to N-acetylneuraminic acid. Furthermore, the present invention provides methods for the large-scale in vivo synthesis of sialylated compounds by culturing microorganisms in a culture medium optionally comprising exogenous precursors such as, but not limited to, lactose, lacto-N-biose, N-acetyllactosamine and / or aglycone, wherein the microorganism dephosphorylates N-acetylglucosamine-6-phosp...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P19/26C12N1/21C12N1/19C12P19/18C12N15/52C12N9/16C12N9/90C12N9/10C12N9/80C12N9/12C12N9/88
CPCC12P19/18C12P19/26C12N9/1029C12N9/1085C12N9/1205C12N9/16C12N9/80C12N9/88C12N9/90C12N15/52C12N15/70
Inventor J·博普雷兹P·库西蒙特D·范赫普G·彼得斯A·瓦考特兰
Owner 因比奥斯公司
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