公开(公告)号：US08293511B2

公开(公告)日：2012-10-23

申请号：US12444108

申请日：2007-10-02

申请人： Marcus Hans ,  Roelof Ary Lans Bovenberg ,  Paul Klaassen ,  Rémon Boer ,  Jan Metske Van Der Laan

发明人： Marcus Hans ,  Roelof Ary Lans Bovenberg ,  Paul Klaassen ,  Rémon Boer ,  Jan Metske Van Der Laan

IPC分类号： C12N9/00 ,  C12P37/00

CPC分类号： C12N9/0004

摘要： The present invention describes a process for the production of an N-α-amino-hydroxyphenylacetyl or an N-α-aminophenylacetyl β-lactam antibiotic comprising an IPNS-catalysed conversion of a precursor tripeptide hydroxyphenylglycyl-cysteinyl-valine (HpgCV) or phenylglycyl-cysteinyl-valine (PgCV), respectively, to the N-hydroxyphenylglycyl or the N-phenylglycyl β-lactam antibiotic, respectively. The tripeptide HpgCV or the tripeptide PgCV may further be prepared by contacting the amino acids hydroxyphenylglycine (Hpg) or phenylglycine (Pg), cystein (C) and valine (V) with a non-ribosomal peptide synthetase (NRPS) to effect formation of the tripeptide HpgCV or the tripeptide PgCV, the NRPS comprising a first module M1 specific for Hpg or Pg, a second module M2 specific for C and a third module M3 specific for V An IPNS is further provided having an improved activity in this conversion, as well as an NRPS catalysing the formation of the tripeptides. Also a host cell is provided capable of fermentatively producing β-lactam antibiotics with N-α-amino-hydroxyphenylacetyl or an N-α-aminophenylacetyl side chains.

摘要翻译： 本发明描述了一种制备N-α-氨基 - 羟基苯基乙酰基或N-α-氨基苯基乙酰基 - 内酰胺抗生素的方法，其包括前体三肽羟基苯基甘氨酰 - 半胱氨酰 - 缬氨酸（HpgCV）或苯基甘氨酰 - 半胱氨酰缬氨酸（PgCV）分别转化为N-羟基苯基甘氨酰或N-苯基甘氨酰和β-内酰胺抗生素。 三肽HpgCV或三肽PgCV可以通过使氨基酸羟基苯基甘氨酸（Hpg）或苯基甘氨酸（Pg），半胱氨酸（C）和缬氨酸（V）与非核糖体肽合成酶（NRPS）接触来进一步制备，以形成 三肽HpgCV或三肽PgCV，NRPS包括特定于Hpg或Pg的第一模块M1，特定于C的第​​二模块M2和特定于V An IPNS的第三模块M3，还具有在该转换中具有改进的活性 作为催化三肽形成的NRPS。 还提供了能够用N-α-氨基 - 羟基苯基乙酰基或N-α-氨基苯乙酰侧链发酵生产β-内酰胺抗生素的宿主细胞。

公开(公告)号：US20100009404A1

公开(公告)日：2010-01-14

申请号：US12444108

申请日：2007-10-02

申请人： Marcus Hans ,  Roelof Ary Lans Bovenberg ,  Paul Klaassen ,  Rémon Boer ,  Jan Metske Van Der Laan

发明人： Marcus Hans ,  Roelof Ary Lans Bovenberg ,  Paul Klaassen ,  Rémon Boer ,  Jan Metske Van Der Laan

IPC分类号： C12P37/00 ,  C12N9/00 ,  C12N15/52 ,  C12N1/21 ,  C12P35/00

CPC分类号： C12N9/0004

摘要： The present invention describes a process for the production of an N-α-amino-hydroxyphenylacetyl or an N-α-aminophenylacetyl β-lactam antibiotic comprising an IPNS-catalysed conversion of a precursor tripeptide hydroxyphenylglycyl-cysteinyl-valine (HpgCV) or phenylglycyl-cysteinyl-valine (PgCV), respectively, to the N-hydroxyphenylglycyl or the N-phenylglycyl β-lactam antibiotic, respectively. The tripeptide HpgCV or the tripeptide PgCV may further be prepared by contacting the amino acids hydroxyphenylglycine (Hpg) or phenylglycine (Pg), cystein (C) and valine (V) with a non-ribosomal peptide synthetase (NRPS) to effect formation of the tripeptide HpgCV or the tripeptide PgCV, the NRPS comprising a first module M1 specific for Hpg or Pg, a second module M2 specific for C and a third module M3 specific for V An IPNS is further provided having an improved activity in this conversion, as well as an NRPS catalysing the formation of the tripeptides. Also a host cell is provided capable of fermentatively producing β-lactam antibiotics with N-α-amino-hydroxyphenylacetyl or an N-α-aminophenylacetyl side chains.

摘要翻译： 本发明描述了制备N-α-氨基 - 羟基苯基乙酰基或N-α-氨基苯基乙酰基β-内酰胺抗生素的方法，其包括前体三肽羟基苯基甘氨酰 - 半胱氨酰 - 缬氨酸（HpgCV）或苯基甘氨酰 - 半胱氨酰缬氨酸（PgCV）分别分别与N-羟基苯基甘氨酰或N-苯基甘氨酰β-内酰胺抗生素。 三肽HpgCV或三肽PgCV可以通过使氨基酸羟基苯基甘氨酸（Hpg）或苯基甘氨酸（Pg），半胱氨酸（C）和缬氨酸（V）与非核糖体肽合成酶（NRPS）接触来进一步制备，以形成 三肽HpgCV或三肽PgCV，NRPS包括特定于Hpg或Pg的第一模块M1，特定于C的第​​二模块M2和特定于V An IPNS的第三模块M3，还具有在该转换中具有改进的活性 作为催化三肽形成的NRPS。 还提供了能够用N-α-氨基 - 羟基苯基乙酰基或N-α-氨基苯乙酰侧链发酵生产β-内酰胺抗生素的宿主细胞。