Glycosyltransferases for biosynthesis of oligosaccharides, and genes
encoding them
    1.
    发明授权
    Glycosyltransferases for biosynthesis of oligosaccharides, and genes encoding them 失效
    用于寡糖生物合成的糖基转移酶和编码它们的基因

    公开(公告)号:US5798233A

    公开(公告)日:1998-08-25

    申请号:US683458

    申请日:1996-07-18

    摘要: The present invention is directed to nucleic acids encoding glycosyltransferases, the proteins encoded thereby, and to methods for synthesizing oligosaccharides using the glycosyltransferases of the invention. In particular, the present application is directed to identification a glycosyltransferase locus of Neisseria gonorrhoeae containing five open reading frames for five different glycosyltransferases. The functionally active glycosyltransferases of the invention are characterized by catalyzing reactions such as adding Gal .beta.1.fwdarw.4 to GlcNAc or Glc; adding GalNAc or GlcNAc .beta.1.fwdarw.3 to Gal; and adding Gal .alpha.1.fwdarw.4 to Gal. The glycosyltransferases of the invention are particularly suited to the synthesis of the oligosaccharides Gal.beta.1.fwdarw.4GlcNAc .beta.1.fwdarw.3Gal.beta.1.fwdarw.4Glc (a mimic of lacto-N-neotetraose), GalNAc.beta.1.fwdarw.3Gal.beta.l.fwdarw.4GlcNAc.beta.1.fwdarw.3Gal.beta.1.fwdarw.4Glc.beta.1.fwdarw.4 (a mimic ganglioside), and Gal.alpha.1.fwdarw.4Gal.beta.1.fwdarw.4Glc.beta.1.fwdarw.4Hep.fwdarw.R (a mimic of the saccharide portion of globo-glycolipids).

    摘要翻译: 本发明涉及编码糖基转移酶的核酸,由此编码的蛋白质,以及使用本发明的糖基转移酶合成寡糖的方法。 特别地,本申请涉及鉴定含有五个不同糖基转移酶的五个开放阅读框的淋病奈瑟氏球菌的糖基转移酶基因座。 本发明的功能活性糖基转移酶的特征在于催化反应,例如向GlcNAc或Glc加入Galβ1-4; 将GalNAc或GlcNAcβ1-> 3加入Gal; 并将Galα1-> 4加入Gal。 本发明的糖基转移酶特别适用于低聚糖Galβ1-> 4GlcNAcβ1->3Galβ1-> 4Glc(模拟乳-N-新四糖),GalNAcβ1->3Galβ1- > 4GlcNAcβ1->3Galβ1-> 4Glcβ1-> 4(模拟神经节苷脂)和Galα1->4Galβ1-> 4Glcβ1-> 4Hep-> R(模拟糖部分 的糖尿病)。

    Glycosyltransferases for biosynthesis of oligosaccharides, and genes
encoding them
    2.
    发明授权
    Glycosyltransferases for biosynthesis of oligosaccharides, and genes encoding them 失效
    用于寡糖生物合成的糖基转移酶和编码它们的基因

    公开(公告)号:US5705367A

    公开(公告)日:1998-01-06

    申请号:US683426

    申请日:1996-07-18

    摘要: The present invention is directed to nucleic acids encoding glycosyltransferases, the proteins encoded thereby, and to methods for synthesizing oligosaccharides using the glycosyltransferases of the invention. In particular, the present application is directed to identification a glycosyltransferase locus of Neisseria gonorrhoeae containing five open reading frames for five different glycosyltransferases. The functionally active glycosyltransferases of the invention are characterized by catalyzing reactions such as adding Gal .beta..fwdarw.4 to GlcNAc or Glc; adding GalNAc or GlcNAc .beta.1.fwdarw.3 to Gal; and adding Gal .alpha.1.fwdarw.4 to Gal. The glycosyltransferases of the invention are particularly suited to the synthesis of the oligosaccharides Gal.beta.1.fwdarw.4GlcNAc.beta.1.fwdarw.3Gal.beta.1.fwdarw.4Glc (a mimic of lacto-N-neotetraose), GalNAc.beta.1.fwdarw.3Gal.beta.1.fwdarw.4GlcNAc.beta.1.fwdarw.3Gal.beta.1.fwdarw.4Glc.beta.1.fwdarw.4 (a mimic ganglioside), and Gal.alpha.1.fwdarw.4Gal.beta.1.fwdarw.4Glc.beta.1.fwdarw.4Hep.fwdarw.R (a mimic of the saccharide portion of globo-glycolipids).

    摘要翻译: 本发明涉及编码糖基转移酶的核酸,由此编码的蛋白质,以及使用本发明的糖基转移酶合成寡糖的方法。 特别地,本申请涉及鉴定含有五个不同糖基转移酶的五个开放阅读框的淋病奈瑟氏球菌的糖基转移酶基因座。 本发明的功能活性糖基转移酶的特征在于催化反应,例如向GlcNAc或Glc加入Galβ→4; 将GalNAc或GlcNAcβ1-> 3加入Gal; 并将Galα1-> 4加入Gal。 本发明的糖基转移酶特别适用于合成低聚糖Galβ1-> 4GlcNAcβ1->3Galβ1-> 4Glc(模拟乳-N-新四糖),GalNAcβ1->3Galβ1- > 4GlcNAcβ1->3Galβ1-> 4Glcβ1-> 4(模拟神经节苷脂)和Galα1->4Galβ1-> 4Glcβ1-> 4Hep-> R(模拟糖部分 的糖尿病)。

    Modified hexa-acylated neisserial LPS

    公开(公告)号:US11292808B2

    公开(公告)日:2022-04-05

    申请号:US16072895

    申请日:2017-01-27

    摘要: The present invention relates to neisserial LPS having a hexa-acylated lipid A moiety, wherein the hexa-acylated lipid A moiety is modified as compared to the lipid A moiety of a wild-type neisserial LPS in that it comprises a palmitoleoyl instead of a lauroyl secondary acyl chain on the glucosamine at the non-reducing end of the lipid A moiety. The invention further relates to mixtures of the hexa-acylated LPS with the corresponding penta-acylated LPS, lacking a secondary acyl chain on the glucosamine at the non-reducing end of the lipid A moiety. The invention also relates to neisserial bacteria that have been genetically modified to reduce expression of the endogenous lpxL1 gene and to introduce expression of a heterologous thermosensitive lpxP gene for producing the hexa- and penta-acylated LPS. By selecting the time and/or temperature at which the bacterium is grown, it is feasible to increase or decrease the amount of hexa-acylated lipid A structure relative to the corresponding penta-acylated structure and thereby modulate the TLR4 agonist activity of the neisserial LPS of the invention, to the exact level of activity required for a particular immunotherapeutic approach.