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1. 发明申请

US20080254523A1 Methods for the Production of Products in Host Cells 审中-公开
标题翻译：宿主细胞产品的生产方法
公开(公告)号：US20080254523A1
公开(公告)日：2008-10-16
申请号：US12038373
申请日：2008-02-27
申请人： Timothy C. Dodge , Fernando Valle
发明人： Timothy C. Dodge , Fernando Valle
IPC分类号： C12P7/58
CPC分类号： C12N15/52 , C12P7/46 , C12P7/60 , C12P19/02
摘要： The invention provides methods and host cells for the production of ascorbic acid intermediates. The invention also provides host cells having a modification in a polynucleotide that uncouples the catabolic pathway from the oxidative pathway by deleting the encoding for an endogenous enzymatic activity that phosphorylates D-glucose at its 6th carbon and/or a polynucleotide that has deleted the encoding for endogenous enzymatic activity that phosphorylates D-gluconate at its 6th carbon. Such host cells are used for the production of products, such as, ascorbic acid intermediates. Nucleic acid and amino acid sequences with inactivated enzymatic activity which phosphorylates D-glucose at its 6th carbon and inactivated enzymatic activity which phosphorylates D-gluconate at its 6th carbon are provided.
摘要翻译：本发明提供了用于生产抗坏血酸中间体的方法和宿主细胞。本发明还提供了在多核苷酸中具有修饰的宿主细胞，其通过缺失在其第6个碳上磷酸化D-葡萄糖的内源性酶活性和/或已经缺失编码的多核苷酸的编码来解离分解代谢途径从氧化途径在其第6个碳上磷酸化D-葡萄糖酸的内生酶活性。这样的宿主细胞用于生产产品，如抗坏血酸中间体。提供具有灭活的酶活性的核酸和氨基酸序列，其在其第6个碳上磷酸化D-葡萄糖，并且在其第6个碳上磷酸化D-葡萄糖酸盐的失活的酶活性。

2. 发明授权

US07419795B2 Metabolically engineered bacterial strains having non-functional endogenous gluconate transporters 失效
标题翻译：具有非功能性内源葡萄糖酸盐转运蛋白的代谢改造的细菌菌株
公开(公告)号：US07419795B2
公开(公告)日：2008-09-02
申请号：US10842929
申请日：2004-05-10
申请人： Timothy C. Dodge , Manoj Kumar , M. Harunur Rashid , Fernando Valle
发明人： Timothy C. Dodge , Manoj Kumar , M. Harunur Rashid , Fernando Valle
IPC分类号： G01N33/53
CPC分类号： C12P7/58 , C07K14/24 , C12P7/60
摘要： The present invention relates to engineering metabolic pathways in bacterial host cells which results in enhanced carbon flow for the production of ascorbic acid (ASA) intermediates. In particular, the invention relates to increasing the production of ASA intermediates in bacterial cells by enhancing the availability of gluconate resulting from the inactivation of endogenous gluconate transporter genes.
摘要翻译：本发明涉及在细菌宿主细胞中工程代谢途径，其导致用于生产抗坏血酸（ASA）中间体的增强的碳流。特别地，本发明涉及通过增加由内源性葡萄糖酸转运蛋白基因失活产生的葡萄糖酸盐的可利用性来增加细菌细胞中ASA中间体的产生。

3. 发明申请

US20080299614A1 Metabolically Engineered Bacterial Strains Having Non-Functional Endogenous Gluconate Transporters 有权
标题翻译：具有非功能性内源葡萄糖酸盐转运蛋白的代谢工程细菌菌株
公开(公告)号：US20080299614A1
公开(公告)日：2008-12-04
申请号：US12141522
申请日：2008-06-18
申请人： Timothy C. Dodge , Manoj Kumar , M. Harunur Rashid , Fernando Valle
发明人： Timothy C. Dodge , Manoj Kumar , M. Harunur Rashid , Fernando Valle
IPC分类号： C12P21/04 , C12N1/20 , C12N15/87 , C12N15/11 , C07K14/00
CPC分类号： C12P7/58 , C07K14/24 , C12P7/60
摘要： The present invention relates to engineering metabolic pathways in bacterial host cells which results in enhanced carbon flow for the production of ascorbic acid (ASA) intermediates. In particular, the invention relates to increasing the production of ASA intermediates in bacterial cells by enhancing the availability of gluconate resulting from the inactivation of endogenous gluconate transporter genes.
摘要翻译：本发明涉及在细菌宿主细胞中工程代谢途径，其导致用于生产抗坏血酸（ASA）中间体的增强的碳流。特别地，本发明涉及通过增加由内源性葡萄糖酸转运蛋白基因失活产生的葡萄糖酸盐的可利用性来增加细菌细胞中ASA中间体的产生。

4. 发明授权

US08034583B2 Metabolically engineered bacterial strains having non-functional endogenous gluconate transporters 有权
标题翻译：具有非功能性内源葡萄糖酸盐转运蛋白的代谢改造的细菌菌株
公开(公告)号：US08034583B2
公开(公告)日：2011-10-11
申请号：US12141522
申请日：2008-06-18
申请人： Timothy C. Dodge , Manoj Kumar , M. Harunur Rashid , Fernando Valle
发明人： Timothy C. Dodge , Manoj Kumar , M. Harunur Rashid , Fernando Valle
IPC分类号： C12P21/06
CPC分类号： C12P7/58 , C07K14/24 , C12P7/60
摘要： The present invention relates to engineering metabolic pathways in bacterial host cells which results in enhanced carbon flow for the production of ascorbic acid (ASA) intermediates. In particular, the invention relates to increasing the production of ASA intermediates in bacterial cells by enhancing the availability of gluconate resulting from the inactivation of endogenous gluconate transporter genes.
摘要翻译：本发明涉及在细菌宿主细胞中工程代谢途径，其导致用于生产抗坏血酸（ASA）中间体的增强的碳流。特别地，本发明涉及通过增加由内源性葡萄糖酸转运蛋白基因失活产生的葡萄糖酸盐的可利用性来增加细菌细胞中ASA中间体的产生。

5. 发明授权

US07033804B2 Methods for the production of products in host cells 有权
公开(公告)号：US07033804B2
公开(公告)日：2006-04-25
申请号：US10116821
申请日：2002-04-04
申请人： Timothy C. Dodge , Fernando Valle
发明人： Timothy C. Dodge , Fernando Valle
IPC分类号： C12P7/60 , C12P7/58
CPC分类号： C12N15/52 , C12P7/46 , C12P7/60 , C12P19/02
摘要： The invention provides methods and host cells for the production of ascorbic acid intermediates. The invention also provides host cells having a modification in a polynucleotide that uncouples the catabolic pathway from the oxidative pathway by deleting the encoding for an endogenous enzymatic activity that phosphorylates D-glucose at its 6th carbon and/or a polynucleotide that has deleted the encoding for endogenous enzymatic activity that phosphorylates D-gluconate at its 6th carbon. Such host cells are used for the production of products, such as, ascorbic acid intermediates. Nucleic acid and amino acid sequences with inactivated enzymatic activity which phosphorylates D-glucose at its 6th carbon and inactivated enzymatic activity which phosphorylates D-gluconate at its 6th carbon are provided.

6. 发明申请

US20120009635A1 Metabolically Engineered Bacterial Strains Having Non-Functional Endogenous Gluconate Transporters 审中-公开
标题翻译：具有非功能性内源葡萄糖酸盐转运蛋白的代谢工程细菌菌株
公开(公告)号：US20120009635A1
公开(公告)日：2012-01-12
申请号：US13228833
申请日：2011-09-09
申请人： Timothy C. Dodge , Manoj Kumar , M. Harunur Rashid , Fernando Valle
发明人： Timothy C. Dodge , Manoj Kumar , M. Harunur Rashid , Fernando Valle
IPC分类号： C12P17/04 , C07K14/24 , C12N1/21 , C12N15/31 , C12P7/60 , C12P7/58
CPC分类号： C12P7/58 , C07K14/24 , C12P7/60
摘要： The present invention relates to engineering metabolic pathways in bacterial host cells which results in enhanced carbon flow for the production of ascorbic acid (ASA) intermediates. In particular, the invention relates to increasing the production of ASA intermediates in bacterial cells by enhancing the availability of gluconate resulting from the inactivation of endogenous gluconate transporter genes.
摘要翻译：本发明涉及在细菌宿主细胞中工程代谢途径，其导致用于生产抗坏血酸（ASA）中间体的增强的碳流。特别地，本发明涉及通过增加由内源性葡萄糖酸转运蛋白基因失活产生的葡萄糖酸盐的可利用性来增加细菌细胞中ASA中间体的产生。

7. 发明授权

US07407780B2 Process for producing glycerol in recombinant bacterial host cells 有权
标题翻译：在重组细菌宿主细胞中生产甘油的方法
公开(公告)号：US07407780B2
公开(公告)日：2008-08-05
申请号：US11598375
申请日：2006-11-13
申请人： Timothy C. Dodge , Fernando Valle
发明人： Timothy C. Dodge , Fernando Valle
IPC分类号： C12P17/04 , C12N9/12 , C12N1/20 , C12N15/74 , C07H21/04
CPC分类号： C12N9/1205 , C12N15/52 , C12P7/60 , C12P19/02 , C12P25/00
摘要： The invention provides methods for producing products comprising improved host cells genetically engineered to have uncoupled productive and catabolic pathways. In particular, the present invention provides host cells having a modification in nucleic acid encoding an endogenous enzymatic activity that phosphorylates D-glucose at its 6th carbon and/or a modification of nucleic acid encoding an enzymatic activity that phosphorylates D-gluconate at its 6th carbon. Such improved host cells are used for the production of products, such as, ascorbic acid intermediates. Methods for making and using the improved host cells are provided. Nucleic acid and amino acid sequences for glucokinase and gluconokinase are provided.
摘要翻译：本发明提供了用于生产包含经遗传工程改良的宿主细胞以产生解偶联生产和分解代谢途径的产物的方法。特别地，本发明提供了在编码在其第六个碳上磷酸化D-葡萄糖的内源酶活性的核酸修饰的宿主细胞和/或编码在其第六碳上磷酸化D-葡萄糖酸的酶活性的核酸的修饰。这种改良的宿主细胞用于生产产品，如抗坏血酸中间体。提供了制备和使用改进的宿主细胞的方法。提供了用于葡萄糖激酶和葡糖激酶的核酸和氨基酸序列。

8. 发明授权

US07241587B2 Method of uncoupling the catabolic pathway of glycolysis from the oxidative membrane bound pathway of glucose conversion 有权
标题翻译：将糖酵解的分解代谢途径与葡萄糖转化的氧化膜结合途径解偶联的方法
公开(公告)号：US07241587B2
公开(公告)日：2007-07-10
申请号：US10117283
申请日：2002-04-04
申请人： Timothy C. Dodge , Fernando Valle
发明人： Timothy C. Dodge , Fernando Valle
IPC分类号： C12P1/00 , C12P19/28 , C12N9/10 , C12N1/20 , C07H21/04
CPC分类号： C12N9/1205 , C12N15/52 , C12P7/60 , C12P19/02 , C12P25/00
摘要： The invention provides methods for producing products comprising improved host cells genetically engineered to have uncoupled productive and catabolic pathways. In particular, the present invention provides host cells having a modification in nucleic acid encoding an endogenous enzymatic activity that phosphorylates D-glucose at its 6th carbon and/or a modification of nucleic acid encoding an enzymatic activity that phosphorylates D-gluconate at its 6th carbon. Such improved host cells are used for the production of products, such as, ascorbic acid intermediates. Methods for making and using the improved host cells are provided. Nucleic acid and amino acid sequences for glucokinase and gluconokinase are provided.
摘要翻译：本发明提供了用于生产包含经遗传工程改良的宿主细胞以产生解偶联生产和分解代谢途径的产物的方法。特别地，本发明提供了在编码在其第六个碳上磷酸化D-葡萄糖的内源酶活性的核酸修饰的宿主细胞和/或编码在其第六碳上磷酸化D-葡萄糖酸的酶活性的核酸的修饰。这种改良的宿主细胞用于生产产品，如抗坏血酸中间体。提供了制备和使用改进的宿主细胞的方法。提供了用于葡萄糖激酶和葡糖激酶的核酸和氨基酸序列。

9. 发明授权

US10266832B2 Filamentous fungi having an altered viscosity phenotype 有权
公开(公告)号：US10266832B2
公开(公告)日：2019-04-23
申请号：US13817421
申请日：2011-08-25
申请人： Timothy C. Dodge , Aleksandra Virag , Michael Ward
发明人： Timothy C. Dodge , Aleksandra Virag , Michael Ward
IPC分类号： C12N15/80 , C07K14/37 , C12N1/14 , C12N9/42 , C12N9/34 , C12N9/24
摘要： Described are compositions and methods relating variant filamentous fungi having altered growth characteristics. Such variants are well-suited for growth in submerged cultures, e.g., for the large-scale production of enzymes and other proteins for commercial applications.

10. 发明授权

US06190892B1 Microbial production of indigo 失效
公开(公告)号：US06190892B1
公开(公告)日：2001-02-20
申请号：US08560729
申请日：1995-11-20
申请人： Walter Weyler , Timothy C. Dodge , John J. Lauff , Dan J. Wendt
发明人： Walter Weyler , Timothy C. Dodge , John J. Lauff , Dan J. Wendt
IPC分类号： C07H2104
CPC分类号： H04W24/00 , C12N9/0069 , C12N9/86 , C12N15/52 , C12P17/165 , H04W84/14
摘要： There is provided an improved process for the biosynthetic production of indigo, the improvement comprising removing unwanted by-products such as isatin or indirubin from the broth in which such indigo is produced. Isatin can be removed by enzymatic activity using an isatin-removing enzyme such as an isatin hydrolase, or by other techniques such as process parameters (elevated temperature, pH), or by contacting the broth containing the isatin with appropriate adsorption compounds/compositions such as carbon or appropriate resins. Since isatin is the precursor of indirubin, the indirubin levels are decreased as a result of isatin removal.

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