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1. 发明申请

US20100016170A1 HIGH THROUGHPUT METHOD FOR DISCOVERY OF GENE CLUSTERS 审中-公开
标题翻译：用于发现基因簇的高通量方法
公开(公告)号：US20100016170A1
公开(公告)日：2010-01-21
申请号：US11803406
申请日：2007-05-14
申请人： Chris M. Farnet , Alfredo Staffa , Emmanuel Zazopoulos
发明人： Chris M. Farnet , Alfredo Staffa , Emmanuel Zazopoulos
IPC分类号： C40B20/04
CPC分类号： C07K14/36 , C07K14/365 , C12N15/52 , C12P19/62
摘要： A method for identifying gene cluster is disclosed. The method may be used for identifying gene clusters involved in the biosynthesis of natural products. A small insert library of DNA fragments of genomic DNA and a large insert library of DNA fragments of genomic DNA are prepared. Fragments in the small insert library are sequenced and compared by homology comparison under computer control to a database containing genes, gene fragments or proteins known to be involved in the biosynthesis of microbial natural products. Fragments having similar structure to genes, gene fragments or proteins known to be involved in the biosynthesis of naturally occurring metabolites are used as probes to screen the large insert library of genomic DNA to detect gene clusters involved in the biosynthesis of microbial natural products.
摘要翻译：公开了鉴定基因簇的方法。该方法可用于鉴定涉及天然产物生物合成的基因簇。制备基因组DNA的DNA片段的小插入文库和基因组DNA的DNA片段的大插入文库。对小插入片段中的片段进行测序，并通过计算机控制下的同源性比较与包含已知参与微生物天然产物生物合成的基因，基因片段或蛋白质的数据库进行比较。具有与基因相似结构的片段，已知参与天然存在的代谢物的生物合成的基因片段或蛋白质被用作筛选基因组DNA的大插入文库以探测参与微生物天然产物生物合成的基因簇的片段。

2. 发明授权

US07635765B2 Gene encoding a nonribosomal peptide synthetase for the production of ramoplanin 失效
标题翻译：编码非核糖体多肽合成酶的基因用于产生拉莫拉宁
公开(公告)号：US07635765B2
公开(公告)日：2009-12-22
申请号：US11205109
申请日：2005-08-17
申请人： Chris M. Farnet , Emmanuel Zazopoulos , Alfredo Staffa
发明人： Chris M. Farnet , Emmanuel Zazopoulos , Alfredo Staffa
IPC分类号： C07H21/04 , C07K14/00
CPC分类号： C07K14/365 , C12N15/52
摘要： The present invention relates to isolated genetic sequences encoding nonribosomal peptide synthetase (NRPS) proteins which direct the biosynthesis of the antibiotic ramoplanin in microorganisms such as Actinoplanes sp. The isolated gene sequences serve as substrates for bioengineering of antibiotic structures.
摘要翻译：本发明涉及编码非核糖体肽合成酶（NRPS）蛋白质的分离的遗传序列，其指导抗微生物如抗生素拉莫拉宁的生物合成，例如Actinoplanes sp。分离的基因序列作为抗生素结构生物工程的底物。

3. 发明授权

US07462705B2 Nucleic acids encoding an enediyne polyketide synthase complex 失效
标题翻译：编码烯二酮聚酮化合物复合物的核酸
公开(公告)号：US07462705B2
公开(公告)日：2008-12-09
申请号：US11053576
申请日：2005-02-08
申请人： Chris M. Farnet , Alfredo Staffa , Emmanuel Zazopoulos
发明人： Chris M. Farnet , Alfredo Staffa , Emmanuel Zazopoulos
IPC分类号： C07H21/04
CPC分类号： C07K14/36 , C12N15/52
摘要： Five protein families cooperate to form the warhead structure that characterizes enediyne compounds, both chromoprotein enediynes and non-chromoprotein enediynes. The protein families include a polyketide synthase and thioesterase protein which form a polyketide synthase catalytic complex involved in warhead formation in enediynes. Genes encoding a member of each of the five protein families are found in all enediyne biosynthetic loci. The genes and proteins may be used in genetic engineering applications to design new enediyne compounds and in methods to identify new enediyne biosynthetic loci.
摘要翻译：五个蛋白质家族合作形成弹头结构，其特征是烯雌酮化合物，包括染色体蛋白烯和非色素蛋白烯二烯。蛋白质家族包括聚酮化合物合酶和硫酯酶蛋白，其形成涉及在炔诺酮中形成弹头的聚酮化合物合酶催化复合物。在所有烯二烯生物合成基因座中都发现编码五个蛋白家族中每一个的成员的基因。基因和蛋白质可用于遗传工程应用中以设计新的烯二烯化合物和鉴定新的烯二炔生物合成基因座的方法。

4. 发明授权

US07257562B2 High throughput method for discovery of gene clusters 失效
标题翻译：用于发现基因簇的高通量方法
公开(公告)号：US07257562B2
公开(公告)日：2007-08-14
申请号：US10232370
申请日：2002-09-03
申请人： Chris M. Farnet , Alfredo Staffa , Emmanuel Zazopoulos
发明人： Chris M. Farnet , Alfredo Staffa , Emmanuel Zazopoulos
IPC分类号： G06N3/00 , G01N33/48 , C12Q1/00
CPC分类号： C07K14/36 , C07K14/365 , C12N15/52 , C12P19/62
摘要： A method for identifying gene cluster is disclosed. The method may be used for identifying gene clusters involved in the biosynthesis of natural products. A small insert library of DNA fragments of genomic DNA and a large insert library of DNA fragments of genomic DNA are prepared. Fragments in the small insert library are sequenced and compared by homology comparison under computer control to a database containing genes, gene fragments or proteins known to be involved in the biosynthesis of microbial natural products. Fragments having similar structure to genes, gene fragments or proteins known to be involved in the biosynthesis of naturally occurring metabolites are used as probes to screen the large insert library of genomic DNA to detect gene clusters involved in the biosynthesis of microbial natural products.
摘要翻译：公开了鉴定基因簇的方法。该方法可用于鉴定涉及天然产物生物合成的基因簇。制备基因组DNA的DNA片段的小插入文库和基因组DNA的DNA片段的大插入文库。对小插入片段中的片段进行测序，并通过计算机控制下的同源性比较与包含已知参与微生物天然产物生物合成的基因，基因片段或蛋白质的数据库进行比较。具有与基因相似结构的片段，已知参与天然存在的代谢物的生物合成的基因片段或蛋白质被用作筛选基因组DNA的大插入文库以探测参与微生物天然产物生物合成的基因簇的片段。

5. 发明授权

US07235651B2 Genes and proteins involved in the biosynthesis of lipopeptides 失效
标题翻译：参与脂肽生物合成的基因和蛋白质
公开(公告)号：US07235651B2
公开(公告)日：2007-06-26
申请号：US10329079
申请日：2002-12-24
申请人： Chris M. Farnet , Alfredo Staffa , Emmanuel Zazopoulos
发明人： Chris M. Farnet , Alfredo Staffa , Emmanuel Zazopoulos
IPC分类号： C07H21/02
CPC分类号： C07K14/36 , C12N15/52
摘要： Genes and proteins involved in the biosynthesis of lipopeptides by microorganisms, in particular the nucleic acids forming the biosynthetic locus for the A54145 lipopeptide from Streptomyces fradiae and the A54145-like lipopeptide from Streptomyces refuineus. These nucleic acids can be used to make expression constructs and transformed host cells for the production of lipopeptides. The genes and proteins allow direct manipulation of lipopeptides and related chemical structures via chemical engineering of the proteins involved in the biosynthesis of A54145.
摘要翻译：涉及通过微生物生物合成脂肽的基因和蛋白质，特别是形成来自链霉菌的A54145脂肽的生物合成基因座的核酸和来自链霉菌（Streptomyces refuineus）的A54145样脂肽。这些核酸可用于制备用于产生脂肽的表达构建体和转化的宿主细胞。基因和蛋白质可以通过参与A54145生物合成的蛋白质的化学工程直接操纵脂肽和相关的化学结构。

6. 发明授权

US07078185B2 Gene encoding a nonribosomal peptide synthetase for the production of ramoplanin 失效
标题翻译：编码非核糖体多肽合成酶的基因用于产生拉莫拉宁
公开(公告)号：US07078185B2
公开(公告)日：2006-07-18
申请号：US09976059
申请日：2001-10-15
申请人： Chris M. Farnet , Emmanuel Zazopoulos , Alfredo Staffa
发明人： Chris M. Farnet , Emmanuel Zazopoulos , Alfredo Staffa
IPC分类号： C12P21/06
CPC分类号： C07K14/365 , C12N15/52
摘要： The present invention relates to an isolated genetic sequence encoding a nonribosomal peptide synthetase (NRPS) protein which directs the biosynthesis of the antibiotic ramoplanin in microorganisms such as Actinoplanes sp. The isolated gene sequence serves as a substrate for bioengineering of antibiotic structures.
摘要翻译：本发明涉及编码非核糖体肽合成酶（NRPS）蛋白质的分离的遗传序列，其指导抗微生物的抗生素拉莫拉宁的生物合成，例如Actinoplanes sp。分离的基因序列作为抗生素结构生物工程的底物。

7. 发明授权

US06912470B2 Genes and proteins involved in the biosynthesis of enediyne ring structures 失效
公开(公告)号：US06912470B2
公开(公告)日：2005-06-28
申请号：US10152886
申请日：2002-05-21
申请人： Chris M. Farnet , Alfredo Staffa , Emmanuel Zazopoulos
发明人： Chris M. Farnet , Alfredo Staffa , Emmanuel Zazopoulos
IPC分类号： C12N15/09 , A61K31/27 , A61K31/4748 , A61K31/7048 , A61P35/00 , A61P35/02 , C07D491/08 , C07H17/04 , C07H17/08 , C07K14/36 , C07K16/40 , C12N9/00 , C12N15/31 , C12N15/52 , C12P21/02 , C12Q1/26 , C12Q1/68 , G06F17/30 , G06F19/00 , C07K14/00 , C12N15/30
CPC分类号： C07K14/36 , C12N15/52
摘要： Five protein families cooperate to form the warhead structure that characterizes enediyne compounds, both chromoprotein enediynes and non-chromoprotein enediynes. The protein families include a polyketide synthase and thioesterase protein which form a polyketide synthase catalytic complex involved in warhead formation in enediynes. Genes encoding a member of each of the five protein families are found in all enediyne biosynthetic loci. The genes and proteins may be used in genetic engineering applications to design new enediyne compounds and in methods to identify new enediyne biosynthetic loci.

8. 发明授权

US07312339B2 Polyene oxazoles and processes for their preparation 失效
标题翻译：聚烯恶唑及其制备方法
公开(公告)号：US07312339B2
公开(公告)日：2007-12-25
申请号：US10865767
申请日：2004-06-14
申请人： James B. McAlpine , Chris M. Farnet , Emmanuel Zazopoulos , Nargis Ismail , Brian O. Bachmann
发明人： James B. McAlpine , Chris M. Farnet , Emmanuel Zazopoulos , Nargis Ismail , Brian O. Bachmann
IPC分类号： C07D207/444 , C07D209/48
CPC分类号： C12R1/60 , C07D263/32 , C07D413/12 , C12P17/14
摘要： Polyene oxazoles of the following formula wherein R3 is selected from H and methyl, are disclosed. Such compounds, and pharmaceutically acceptable salts thereof, may be used in the inhibition of tumor cell growth. The polyene oxazoles and their pharmaceutically acceptable salts may be formulated as pharmaceutical compositions with pharmaceutically acceptable carriers for use in the inhibition of tumor cells. The polyene oxazoles may be obtained from strains of Streptomyces sparsogenes, such as strain 022 having deposit number IDAC 270504-04.
摘要翻译：公开了下式的多烯恶唑，其中R 3选自H和甲基。这些化合物及其药学上可接受的盐可用于抑制肿瘤细胞生长。多烯恶唑及其药学上可接受的盐可以配制成具有用于抑制肿瘤细胞的药学上可接受的载体的药物组合物。多烯恶唑可以从天竺葵链霉菌菌株获得，例如具有保藏号IDAC 270504-04的菌株022。

9. 发明授权

US07416868B2 Polyene polyketides, processes for their production and their use as a pharmaceutical 失效
标题翻译：聚烯烃聚合物，其生产方法及其作为药物的用途
公开(公告)号：US07416868B2
公开(公告)日：2008-08-26
申请号：US10760494
申请日：2004-01-21
申请人： Emmanuel Zazopoulos , Chris M. Farnet
发明人： Emmanuel Zazopoulos , Chris M. Farnet
IPC分类号： C12N9/00
CPC分类号： C07H15/203 , C07C215/24 , C07C225/14 , C07C235/28 , C07C237/16 , C07C279/22 , C07C305/14 , C07C2601/10 , C07C2601/14 , C07H15/10 , C07H15/18 , C07H15/26 , C12P7/42 , C12P11/00 , C12P13/001 , C12P13/02 , C12P19/44 , C12R1/465 , Y10S435/886
摘要： This invention relates to a new class of polyene polyketides, their pharmaceutically acceptable salts and derivatives, and to methods for obtaining the compounds. One method of obtaining these compounds is by cultivation of novel strains of Streptomyces aizunensis; another method involves expression of biosynthetic pathway genes in transformed host cells. The present invention further relates to the novel strains of Streptomyces aizunensis used to produce these compounds, to the use of these compounds and their pharmaceutically acceptable salts and derivatives as pharmaceuticals, in particular to their use as inhibitors of fungal cell growth and cancer cell growth. The invention also relates to pharmaceutical compositions comprising these novel polyketides or a pharmaceutically acceptable salts or derivatives thereof. Finally, the invention relates to novel polynucleotide sequences and their encoded proteins, which are involved in the biosynthesis of these novel polyketides.
摘要翻译：本发明涉及新类型的多烯聚酮化合物，其药学上可接受的盐和衍生物，以及获得化合物的方法。获得这些化合物的一种方法是通过培养新的链霉菌链霉菌菌株; 另一种方法涉及在转化的宿主细胞中表达生物合成途径基因。本发明还涉及用于制备这些化合物的新型链霉菌Streptomyces aizunensis菌株，使用这些化合物及其药学上可接受的盐和衍生物作为药物，特别是其作为真菌细胞生长抑制剂和癌细胞生长的用途。本发明还涉及包含这些新型聚酮化合物或其药学上可接受的盐或衍生物的药物组合物。最后，本发明涉及参与这些新型聚酮化合物的生物合成的新型多核苷酸序列及其编码的蛋白质。

10. 发明授权

US07101872B2 Farnesyl dibenzodiazepinone, and processes for its production 有权
标题翻译：法呢基二苯并二氮杂酮及其制备方法
公开(公告)号：US07101872B2
公开(公告)日：2006-09-05
申请号：US10762107
申请日：2004-01-21
申请人： Brian O. Bachmann , James B. McAlpine , Emmanuel Zazopoulos , Chris M. Farnet , Mahmood Piraee
发明人： Brian O. Bachmann , James B. McAlpine , Emmanuel Zazopoulos , Chris M. Farnet , Mahmood Piraee
IPC分类号： C07D243/10 , A61K31/55
CPC分类号： C12N9/93 , A61K38/00 , C07D243/38 , C07D405/06 , C07D405/14 , C12N9/0004 , C12N9/10 , C12N9/12 , C12N9/14 , C12N9/88 , C12N9/90 , C12N15/52 , C12P17/10 , C12R1/29 , Y02A50/473
摘要： This invention relates to a novel farnesylated dibenzodiazepinone, named ECO-04601, its pharmaceutically acceptable salts and derivatives, and to methods for obtaining such compounds. One method of obtaining the ECO-04601 compound is by cultivation of a novel strain of Micromonospora sp., 046-ECO11; another method involves expression of biosynthetic pathway genes in transformed host cells. The present invention further relates to Micromonospora sp. strain 046-ECO11, to the use of ECO-04601 and its pharmaceutically acceptable salts and derivatives as pharmaceuticals, in particular to their use as inhibitors of cancer cell growth, bacterial cell growth, mammalian lipoxygenase, and to pharmaceutical compositions comprising ECO-04601 or a pharmaceutically acceptable salt or derivative thereof. Finally, the invention relates to novel polynucleotide sequences and their encoded proteins, which are involved in the biosynthesis of ECO-04601.
摘要翻译：本发明涉及名为ECO-04601的新型法呢基化二苯并二氮杂酮，其药学上可接受的盐和衍生物，以及获得这些化合物的方法。获得ECO-04601化合物的一种方法是通过培养一种新型的小单孢菌属菌株046-ECO11; 另一种方法涉及在转化的宿主细胞中表达生物合成途径基因。本发明还涉及小单孢菌属应用046-ECO11，使用ECO-04601及其药学上可接受的盐和衍生物作为药物，特别是其作为癌细胞生长抑制剂，细菌细胞生长，哺乳动物脂氧合酶的用途，以及包含ECO-04601或其药学上可接受的盐或衍生物。最后，本发明涉及参与ECO-04601的生物合成的新型多核苷酸序列及其编码的蛋白质。

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