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1. 发明申请

WO2015173247A1 NEW MICROORGANISM AND METHOD FOR THE PRODUCTION OF 1.2-PROPANEDIOL BASED ON NADPH DEPENDENT ACETOL REDUCTASE AND IMPROVED NADPH SUPPLY 审中-公开
标题翻译：用于生产基于NADPH依赖性乙酰胆碱还原酶和改进的NADPH供应的1,2-丙二醇的新型微生物和方法
公开(公告)号：WO2015173247A1
公开(公告)日：2015-11-19
申请号：PCT/EP2015/060487
申请日：2015-05-12
申请人： METABOLIC EXPLORER
发明人： ALIPRANDI, Pascale , NAVARRO, Emilie , RAYNAUD, Céline , BESTEL CORRE, Gwénaëlle , SOUCAILLE, Philippe
IPC分类号： C12P7/18
CPC分类号： C12P7/18 , C12N9/0006 , C12N15/52 , C12N15/74 , C12Y101/01001
摘要： The present invention relates to a recombinant microorganism useful for the production of 1,2-propanediol and process for the preparation of 1,2-propanediol. The microorganism of the invention is modified in a way that the 1,2-propanediol production is improved by enhancing NADPH dependent HAR activity.
摘要翻译：本发明涉及可用于生产1,2-丙二醇的重组微生物和1,2-丙二醇的制备方法。本发明的微生物以通过增强NADPH依赖性HAR活性来改善1,2-丙二醇生产的方式进行改性。

2. 发明申请

WO2009043803A3 INCREASING METHIONINE YIELD 审中-公开
公开(公告)号：WO2009043803A3
公开(公告)日：2009-04-09
申请号：PCT/EP2008/062859
申请日：2008-09-25
申请人： METABOLIC EXPLORER , FIGGE, Rainer , SOUCAILLE, Philippe , BARBIER, Guillaume , BESTEL-CORRE, Gwénaëlle , BOISART, Cédric , CHATEAU, Michel
发明人： FIGGE, Rainer , SOUCAILLE, Philippe , BARBIER, Guillaume , BESTEL-CORRE, Gwénaëlle , BOISART, Cédric , CHATEAU, Michel
IPC分类号： C12P13/12
摘要： Process for the production of methionine or its derivatives by culturing a microorganism in an appropriate culture medium comprising a source of carbon and a source of sulfur. The microorganism and/or the culture medium are modified in such way that the methionine/ carbon source yield is increased. The isolation of methionine or its derivates from the fermentation medium is also described.

3. 发明申请

WO2008040387A1 PROCESS FOR CHROMOSOMAL INTEGRATION AND DNA SEQUENCE REPLACEMENT IN CLOSTRIDIA 审中-公开
标题翻译：染色体整合过程和DNA序列替换在CLOSTRIDIA
公开(公告)号：WO2008040387A1
公开(公告)日：2008-04-10
申请号：PCT/EP2006/066997
申请日：2006-10-03
申请人： METABOLIC EXPLORER , SOUCAILLE, Philippe , FIGGE, Rainer , CROUX, Christian
发明人： SOUCAILLE, Philippe , FIGGE, Rainer , CROUX, Christian
IPC分类号： C12N15/74 , C12N15/90
CPC分类号： C12N15/74
摘要： The present invention is related to a new method for replacing or deleting DNA sequences in Clostridia , with high efficiency, easy to perform and applicable at an industrial level. This method is useful to modify several genetic loci in Clostridia in a routine manner. This method is based on a replicative vector carrying at least two marker genes.
摘要翻译：本发明涉及一种用于在梭菌中替代或缺失DNA序列的新方法，其在工业上具有高效率，易于实施和适用。该方法可用于以常规方式修饰梭菌中的几个遗传基因座。该方法基于携带至少两个标记基因的复制载体。

4. 发明申请

WO2006082252A3 METHOD FOR THE ENZYMATIC PRODUCTION OF ALPHA-KETOBUTYRATE 审中-公开
公开(公告)号：WO2006082252A3
公开(公告)日：2006-08-10
申请号：PCT/EP2006/050722
申请日：2006-02-07
申请人： METABOLIC EXPLORER , FIGGE, Rainer , LUX, Fabien , RAYNAUD, Céline , SOUCAILLE, Philippe
发明人： FIGGE, Rainer , LUX, Fabien , RAYNAUD, Céline , SOUCAILLE, Philippe
IPC分类号： C12P13/06 , C12P7/42
摘要： This invention relates to a process for the enzymatic production of α-ketobutyrate and its derivatives, in particular isoleucine. In the described process α-ketobutyrate is obtained from activated homoserine by γ-elimination. Homoserine is activated to either acylhomoserine or phosphohomoserine using homoserinetransacylase and homoserine kinase, respectively. Subsequently phosphohomoserine and/or acylhomoserine is/are transformed into phosphate or/and acylate, ammonia and α-ketobutyrate through the γ-eliminase activity of cystathionine- γ-synthase and/or acylhomoserine sulfliydrylase and/or phosphohomoserine sulfhydrylase. This reaction is favored by (i) reducing intracellular concentrations of H2S or cysteine, (ii) reducing the access of these two sulfur containing substrates to the enzyme cystathionine-γ- synthase and/or acylhomoserine sulfhydrylase and/or phosphohomoserine sulfliydrylase or (iii) by using cystathionine-γ-synthase and/or acylhomoserine sulfliydrylase and/or phosphohomoserine sulfhydrylase with high γ-elimination and low cystathionine-γ-synthase and/or low acylhomoserine sulfliydrylase and/or low phosphohomoserine sulfhydrylase activity. At least one of these measures is applied in microorganisms, in particular coryneform bacteria and enterobacteria, in which as a consequence α-ketobutyrate and/or its derivatives can be produced in high quantities.

5. 发明申请

WO2005073364A2 MICROORGANISME EVOLUE POUR LA PRODUCTION DE 1,2-PROPANEDIOL 审中-公开
标题翻译：用于生产1,2-丙二醇的高级微生物
公开(公告)号：WO2005073364A2
公开(公告)日：2005-08-11
申请号：PCT/FR2005/000070
申请日：2005-01-12
申请人： METABOLIC EXPLORER , MEYNIAL-SALLES, Isabelle , GONZALEZ, Benjamin , SOUCAILLE, Philippe
发明人： MEYNIAL-SALLES, Isabelle , GONZALEZ, Benjamin , SOUCAILLE, Philippe
IPC分类号： C12N1/21
CPC分类号： C12P7/18 , C12N9/0051 , C12N15/01 , C12P7/28
摘要： La présente invention concerne un nouveau procédé de préparation d'une souche de microorganismes évolués pour la production de 1,2-propanediol par métabolisme d'une source de carbone simple, ledit procédé comprenant la culture sous pression de sélection dans un milieu de culture approprié comprenant une source de carbone simple, d'une souche bactérienne initiale comprenant une délétion du gène tpiA et une délétion d'au moins un gène impliqué dans la conversion du méthyl glyoxal (propanal) en lactate, afin de faire évoluer dans ladite souche initiale un ou plusieurs gènes impliqués dans la voie de biosynthèse du DHAP en méthylglyoxal puis en 1,2-propanediol vers des gènes évolués ayant une activité « 1,2-propanediol synthase » améliorée, puis on sélectionne et on isole la ou les souches de microorganismes évolués ayant une activité « 1,2propanediol synthase » améliorée. L'invention concerne également les microorganismes initiaux et les microorganismes évolués ainsi obtenus et un procédé de préparation de 1,2-propanediol et éventuellement d'acétone par culture des microorganismes évolués.
摘要翻译：本发明涉及一种制备用于通过简单碳源代谢制备1,2-丙二醇的先进微生物菌株的新方法，该简单碳源包括在适当的培养基中选择的压力下制备培养物，所述培养基包括简单的碳源，初始含有tpiA基因缺失的细菌菌株和参与乙二醛甲基（丙醛）转化成乳酸盐的至少一个基因的缺失，以便在所述初始菌株中产生一种或多种参与DHPA生物合成甲基乙二醛的基因，然后进入对于表现出改进的1,2-丙二醇合酶活性的先进基因，随后选择展示所述改进的1,2-丙二醇合酶活性的先进微生物菌株。还公开了初始微生物，从而获得了先进的微生物和通过高级微生物培养物制备1,2-丙二醇和可能的丙酮的方法。

6. 发明申请

WO2012001003A1 METHOD FOR THE PREPARATION OF HYDROXY ACIDS 审中-公开
标题翻译：制备羟基酸的方法
公开(公告)号：WO2012001003A1
公开(公告)日：2012-01-05
申请号：PCT/EP2011/060836
申请日：2011-06-28
申请人： METABOLIC EXPLORER , SOUCAILLE, Philippe , BOISART, Cédric
发明人： SOUCAILLE, Philippe , BOISART, Cédric
IPC分类号： C12N9/02 , C12N9/88 , C12P7/04
CPC分类号： C12P7/42 , C12N9/0008 , C12N9/88 , C12N15/63 , C12P7/52
摘要： The present invention concerns a modified microorganism for the biological preparation of an hydroxy acid of formula (I) wherein the microorganism comprises a two-step metabolic pathway for the production of the said hydroxy acid from a hydroxy keto-acid of formula (II) through an intermediate hydroxy-aldehyde of formula (III), wherein EA1 is an enzyme having a 2-keto-acid decarboxylase activity,and EA2 is an enzyme having hydroxy aldehyde dehydrogenase activity. The invention also concerns a method for the fermentative production of a hydroxy acid.
摘要翻译：本发明涉及用于生物制备式（I）的羟基酸的改性微生物，其中微生物包含用于由式（II）的羟基酮酸生成所述羟基酸的两步代谢途径，通过式（III）的中间体羟基醛，其中EA1是具有2-酮酸脱羧酶活性的酶，EA2是具有羟基醛脱氢酶活性的酶。本发明还涉及发酵生产羟基酸的方法。

7. 发明申请

WO2011157728A8 USE OF INDUCIBLE PROMOTERS IN THE PRODUCTION OF GLYCOLIC ACID 审中-公开
公开(公告)号：WO2011157728A8
公开(公告)日：2011-12-22
申请号：PCT/EP2011/059884
申请日：2011-06-15
申请人： METABOLIC EXPLORER , DISCHERT, Wanda , FIGGE, Rainer , SOUCAILLE, Philippe
发明人： DISCHERT, Wanda , FIGGE, Rainer , SOUCAILLE, Philippe
IPC分类号： C12P7/42
摘要： The present invention relates to use of inducible promoters in the production of glycolic acid by fermentation. The present invention concerns a method for the production of glycolic acid in a fermentative process comprising the following steps: -culturing a modified microorganism in an appropriate culture medium comprising a source of carbon, -modulating in said microorganism the expression of a target gene with an external stimulus,and -recovering glycolic acid from the culture medium, wherein in said modified microorganism, the expression of at least one gene involved in glycolic acid production is under the control of a heterologous inducible promoter whose activity is modulated with said external stimulus. The invention also concerned the modified microorganism used in the method of glycolic acid production.

8. 发明申请

WO2011042434A1 1,3-PROPANEDIOL PRODUCTION WITH IMMOBILISED CELLS REACTORS 审中-公开
标题翻译：具有固定化细胞反应器的1,3-丙二醇生产
公开(公告)号：WO2011042434A1
公开(公告)日：2011-04-14
申请号：PCT/EP2010/064825
申请日：2010-10-05
申请人： METABOLIC EXPLORER , CHATEAU, Michel , SOUCAILLE, Philippe , DUBOIS, Jean-Yves
发明人： CHATEAU, Michel , SOUCAILLE, Philippe , DUBOIS, Jean-Yves
IPC分类号： C12P7/18
CPC分类号： C12P7/18
摘要： The present invention concerns a new method for the fermentative production of 1,3-propanediol from glycerol comprising culturing immobilized microorganism on a culture medium with high glycerine content, wherein the microorganism is a Clostridium species, modified for an improved production of 1,3-propanediol.
摘要翻译：本发明涉及从甘油发酵生产1,3-丙二醇的新方法，其包括在具有高甘油含量的培养基上培养固定化的微生物，其中微生物是梭菌属物种，丙二醇。

9. 发明申请

WO2011012702A1 MUTANT GLYCEROL DEHYDROGENASE (GLYDH) FOR THE PRODUCTION OF A BIOCHEMICAL BY FERMENTATION 审中-公开
标题翻译： MUTANT GLYCEROL DEHYDROGENASE（GLYDH）for the Production of A BIOCHEMICAL BY FERMENTATION
公开(公告)号：WO2011012702A1
公开(公告)日：2011-02-03
申请号：PCT/EP2010/061129
申请日：2010-07-30
申请人： METABOLIC EXPLORER , VOELKER, François , DUMON-SEIGNOVERT, Laurence , MEYNIAL-SALLES, Isabelle , SOUCAILLE, Philippe
发明人： VOELKER, François , DUMON-SEIGNOVERT, Laurence , MEYNIAL-SALLES, Isabelle , SOUCAILLE, Philippe
IPC分类号： C12N15/53 , C12N1/21 , C12N9/04 , C12P7/18 , C12Q1/32 , C07C29/60
CPC分类号： C12P7/18 , C12N9/0006
摘要： The present invention concerns a method for the production of 1,2-propanediol, comprising culturing a micro organism modified for an improved production of 1,2- propanediol in an appropriate culture medium and recovery of the 1,2-propanediol which may be further purified wherein the microorganism expresses a glycerol dehydrogenase (GlyDH) enzyme the inhibition of which activity by NAD+ and/or its substrate and/or its product is reduced. The present invention also relates to a mutant glycerol dehydrogenase(Gly DH) comprising at least one amino acid residue in the protein sequence of the parent enzyme replaced by a different amino acid residue at the same position wherein - the mutant enzyme has retained more than 50% of the glycerol dehydrogenase activity of the parent enzyme and - the glycerol dehydrogenase activity of the mutant GlyDH is less inhibited by NAD+ and/or by its substrate as compared to the parent enzyme and/or by its product as compared to the parent enzyme.
摘要翻译：本发明涉及一种生产1,2-丙二醇的方法，该方法包括培养在合适的培养基中改进生产1,2-丙二醇的微生物，并回收可以进一步的1,2-丙二醇纯化，其中微生物表达甘油脱氢酶（GlyDH）酶，减少NAD +和/或其底物和/或其产物对哪种活性的抑制。本发明还涉及包含在相同位置被不同氨基酸残基替换的母体酶的蛋白质序列中的至少一个氨基酸残基的突变体甘油脱氢酶（Gly DH），其中突变体酶保留超过50个亲本酶的甘油脱氢酶活性的百分比和 - 与亲本酶相比，与母体酶和/或其产物相比，突变体GlyDH的甘油脱氢酶活性比NAD +和/或其底物抑制较少。

10. 发明申请

WO2011012693A1 MUTANT METHYLGLYOXAL SYNTHASE (MGS) FOR THE PRODUCTION OF A BIOCHEMICAL BY FERMENTATION 审中-公开
标题翻译：用于通过发酵生产生物化学的突变甲基合成酶（MGS）
公开(公告)号：WO2011012693A1
公开(公告)日：2011-02-03
申请号：PCT/EP2010/061094
申请日：2010-07-30
申请人： METABOLIC EXPLORER , VOELKER, François , DUMON-SEIGNOVERT, Laurence , SOUCAILLE, Philippe
发明人： VOELKER, François , DUMON-SEIGNOVERT, Laurence , SOUCAILLE, Philippe
IPC分类号： C12N9/00 , C12N9/88 , C12N15/00 , C12P7/02 , C12P7/56
CPC分类号： C12N9/88 , C12P7/18 , C12P7/26 , C12P7/56
摘要： The present invention concerns a method for the production of a biochemical selected among lactic acid, acetol and 1,2-propanediol, comprising culturing a microorganism modified for an improved production of the biochemical selected among lactic acid, acetol and 1,2-propanediol in an appropriate culture medium and recovery of the desired biochemical which may be further purified wherein the microorganism expresses a methylglyoxal synthase (MGS) enzyme which activity is not inhibited by orthophosphate. The present invention concerns a mutant methylglyoxal synthase (MGS) comprising at least one amino acid residue in the protein sequence of the parent enzyme replaced by a different amino acid residue at the same position wherein - the mutant enzyme has retained more than 50% of the methylglyoxal synthase activity of the parent enzyme and - the methylglyoxal synthase activity of the mutant MGS is not inhibited by orthophosphate as compared to the parent enzyme.
摘要翻译：本发明涉及一种生产选自乳酸，丙酮醇和1,2-丙二醇的生物化学品的方法，其中包括培养一种微生物，该微生物被改性以提高乳酸，丙酮醇和1,2-丙二醇的生物化学生产合适的培养基和回收期望的生物化学物质，其可以进一步纯化，其中微生物表达甲基乙二醛合酶（MGS）酶，其活性不被正磷酸盐抑制。本发明涉及一种突变体甲基乙二醛合酶（MGS），其包含在相同位置被不同氨基酸残基替换的母体酶蛋白质序列中的至少一个氨基酸残基，其中 - 突变酶保留超过50％与母体酶相比，母体酶的甲基乙二醛合酶活性和 - 突变体MGS的甲基乙二醛合酶活性不被正磷酸盐抑制。

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