公开(公告)号：EP0944729A1

公开(公告)日：1999-09-29

申请号：EP97954433.0

申请日：1997-12-15

申请人： DSM N.V.

发明人： BOVENBERG, Roelof, Ary, Lans

IPC分类号： C12P35 ,  C12P37 ,  C12R1

CPC分类号： C12P37/00

摘要： The present invention discloses a fermentative process for the production of penicillin G or V or cephalosporin G or V derivatives wherein certain derivatives of phenylbutyric acid are used as a side chain precursor. In said phenylbutyric acid derivatives, the acyl chain is extended by pairs of carbon atoms and certain substituents are present at the φ- and/or φ-1 position. The corresponding phenoxybutyric acid derivatives are used to produce penicillin V or cephalosporin V derivatives. Optionally, the penicillin or cephalosporin G or V compounds are deacylated to produce their deacylated counterparts.

公开(公告)号：EP1226266A2

公开(公告)日：2002-07-31

申请号：EP00979601.2

申请日：2000-11-03

申请人： DSM N.V.

发明人： BERG, VAN DEN, Marco, Alexander ,  BOVENBERG, Roelof, Ary, Lans ,  DRIESSEN, Arnold, Jacob, Mattieu ,  KONINGS, Wilhelmus, Nicolaas ,  SCHUURS, Theo, Auke ,  NIEBOER, Maarten ,  WESTERLAKEN, Ilja

IPC分类号： C12P17/18 ,  C12P35/00 ,  C12P37/00 ,  C12N9/12 ,  C12N9/14 ,  C07K14/385 ,  C12N15/31

CPC分类号： C07K14/385 ,  C12P37/00

摘要： An method for enhancing the secretion of a β-lactam compound from a micro-organism is described, together with an isolated polynucleotide encoding the ABC transporter protein responsible for said enhanced secretion. Furthermore an isolated poylnucleotide encoding an ABC transporter is claimed. Method for producing β-lactam compounds in a micro-organism comprising the step of enhancing ABC-transporter activity of said micro-organism and subsequently culturing said micro-organism under conditions allowing the production of said β-lactam compounds is also disclosed.

公开(公告)号：EP1179071A2

公开(公告)日：2002-02-13

申请号：EP00931260.4

申请日：2000-05-22

申请人： DSM N.V.

发明人： BOVENBERG, Roelof, Ary, Lans ,  VAN DEN BERG, Marco, Alexander ,  NIEBOER, Maarten ,  VEENHUIS, Marten ,  KIEL, Jan, Andries, Kornelis, Willem ,  VAN DER KLEI, Ida, Johanna

IPC分类号： C12N15/31 ,  C12N15/80 ,  C12N1/19 ,  C07K14/385 ,  C12P37/00

CPC分类号： C12R1/78 ,  C07K14/37 ,  C07K14/385 ,  C12N15/80 ,  C12P37/00 ,  C12R1/82

摘要： The present invention relates to a method for modulating the production of secondary metabolites in the fungus Penicillium chrysogenum by influencing the homeostasis of organelles by modulating a least one gene which is directly related to organelle homeostasis in this fungus. Preferably, the organelle homeostasis is modulated by genetically engineering at least one gene encoding a protein which is responsible for organelle biogenesis (the expression and/or activity of which is to be increased) and/or at least one gene encoding a protein which is responsible for organelle degeneration (the expression and/or activity of which is to be decreased). Genes involved in organelle biosynthesis in P. chrysogenum are exemplified by the so-called pex11 gene. Genes involved in organelle degradation are exemplified by the so-called vps15 and pdd1 genes.

公开(公告)号：EP1141372A2

公开(公告)日：2001-10-10

申请号：EP99964657.3

申请日：1999-12-21

申请人： DSM N.V.

发明人： BOVENBERG, Roelof, Ary, Lans ,  KERKMAN, Richard ,  KOENHEN, Eric

IPC分类号： C12P35/00

CPC分类号： C12P35/00 ,  C12N9/1029

摘要： The present invention discloses a process for the production of 7-amino cephalosporanic acid (7-ACA) or a derivative thereof comprising the steps of fermenting a P. chrysogenum strain being transformed with an expression construct comprising a nucleotide sequence encoding expandase, hydroxylase and acetyltransferase activity in the presence of a suitable acyl side chain precursor, or a salt or ester thereof, such that an N-acylated 7-ACA compound is produced, N-deacylating the thus produced N-acylated 7-ACA compound and, optionally, acylating the free amino group and/or substituting the 3' acetate group with a side chain suitable to form a cephalosporin antibiotic, characterised in that the nucleotide sequence encoding the acetyltransferase is derived from Acremonium chrysogenum and starts at the second ATG of the open reading frame as present in said nucleotide sequence.

摘要翻译： 本发明公开了生产7-氨基头孢菌酸（7-ACA）或其衍生物的方法，其包括发酵产黄青霉菌菌株的步骤，所述产黄青霉菌菌株用包含编码扩环酶，羟化酶和乙酰​​转移酶的核苷酸序列的表达构建体转化 在合适的酰基侧链前体或其盐或酯存在下的活性，从而产生N-酰化的7-ACA化合物，将由此产生的N-酰化的7-ACA化合物N-脱酰基化，和任选地酰化 游离氨基和/或用适于形成头孢菌素抗生素的侧链取代3'乙酸酯基团，其特征在于编码乙酰转移酶的核苷酸序列来自Acremonium chrysogenum并开始于开放阅读框的第二个ATG， 存在于所述核苷酸序列中。

公开(公告)号：EP0711348B1

公开(公告)日：2003-03-19

申请号：EP94926136.6

申请日：1994-07-29

申请人： DSM N.V.

发明人： BOVENBERG, Roelof, Ary, Lans ,  KOEKMAN, Bertus, Pieter ,  HOEKEMA, Andreas ,  VAN DER LAAN, Jan, Metske ,  VERWEIJ, Jan ,  DE VROOM, Erik

IPC分类号： C12N15/52 ,  C12N1/15 ,  C12N15/80 ,  C12N15/55 ,  C12N9/48 ,  C12P35/00 ,  C12N9/00

CPC分类号： C12N9/0071 ,  C12N9/48 ,  C12N15/80 ,  C12P35/00

摘要： An overall efficient process for the preparation and recovery of 7-aminodesacetoxycephalosporanic acid (7-ADCA) via 3-(carboxyethylthio)propionyl-7-ADCA, using a Penicillium chrysogenum transformant strain expressing expandase in conjunction with acyltransferase, is provided.

公开(公告)号：EP0915988B1

公开(公告)日：2003-01-29

申请号：EP98929264.4

申请日：1998-04-22

申请人： DSM N.V.

发明人： NIEBOER, Maarten ,  DE VROOM, Erik ,  LUGTENBURG, Johannis ,  SCHIPPER, Dirk ,  VOLLEBREGT, Adrianus, Wilhelmus, Hermanus ,  BOVENBERG, Roelof, Ary, Lans

IPC分类号： C12P35/00 ,  C12P37/04 ,  C12N15/52 ,  C12N15/54

CPC分类号： C12N9/0071 ,  C12N9/1029 ,  C12P35/00 ,  C12P37/04 ,  Y10S435/935

摘要： The present invention discloses a process for the production of N-deacylated cephalosporin compounds via the fermentative production of their 7-acylated counterparts.

公开(公告)号：EP0828850B1

公开(公告)日：2001-11-21

申请号：EP96917498.6

申请日：1996-06-03

申请人： DSM N.V.

发明人： BOVENBERG, Roelof, Ary, Lans ,  KOEKMAN, Bertus, Pieter ,  SCHIPPER, Dirk ,  VOLLEBREGT, Adrianus, Wilhelmus, Hermanus

IPC分类号： C12P35/00

CPC分类号： C12N9/0071 ,  C12P35/00

摘要： An overall process for the preparation and recovery of 7-aminodesacetoxycephalosporanic acid (7-ADCA) via enzymatic ring expansion activity on penicillin G, using a Penicillium chrysogenum transformant strain expressing expandase.

公开(公告)号：EP1078069A2

公开(公告)日：2001-02-28

申请号：EP99925015.2

申请日：1999-05-19

申请人： DSM N.V.

发明人： NIEBOER, Maarten ,  BOVENBERG, Roelof, Ary, Lans

IPC分类号： C12N15/53 ,  C12N9/02 ,  C12N1/15 ,  C12P35/00

CPC分类号： C12N9/0071 ,  C12P35/00

摘要： The invention provides DNA, heterologous host cells capable of transcribing, translating or expressing said DNA and methods employing such host cells and cultures thereof for an improved in vivo production of acylated cephalosporins with higher yield. According to the invention, a host cell is provided comprising an enzyme having expandase activity which is predominantly localised in the cytosol (as opposed to localised mainly in or with the peroxisomes or microbodies) of the host cell.

公开(公告)号：EP0979294A2

公开(公告)日：2000-02-16

申请号：EP98924103.9

申请日：1998-04-09

申请人： DSM N.V.

发明人： SELTEN, Gerardus, Cornelis, Maria ,  SWINKELS, Bart, Willem ,  BOVENBERG, Roelof, Ary, Lans

IPC分类号： C12N15/80 ,  C12N15/65 ,  C12N15/52 ,  C12N1/15

CPC分类号： C12N9/16 ,  C12N9/00 ,  C12N15/62 ,  C12N15/80

摘要： The present invention relates to filamentous fungi that comprise in their genomes at last two substantially homologous DNA domains which are suitable for integration of one or more copies of a recombinant DNA molecule and wherein at least two of these DNA domains comprise an integrated copy of a recombinant DNA molecule. The invention also relates to methods for preparing such filamentous fungi and for further multiplying the DNA domains with integrated recombinant DNA molecules through gene conversion or amplification.