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    Preparation of a macrocyclic lactone
    1.
    发明授权
    Preparation of a macrocyclic lactone 失效
    制备大环内酯

    公开(公告)号：US06808903B1

    公开(公告)日：2004-10-26

    申请号：US10129853

    申请日：2002-05-08

    申请人： Johannes Paul Pachlatko ,  Thomas Pitterna ,  Volker Jungmann

    发明人： Johannes Paul Pachlatko ,  Thomas Pitterna ,  Volker Jungmann

    IPC分类号： C12P1962

    CPC分类号： C07H17/08 ,  C12P19/62 ,  C12P19/623 ,  Y02P20/55

    摘要： Subject of the invention is a process for the preparation of a compound of formula (I) in which R1-R9 represent, independently of each other hydrogen a substituent; m is 0, 1 or 2; n is 0, 1, 2 or 3; and the bonds marked with A, B, C, D, E and F indicate, independently of each other, that two adjacent carbon atoms are connected by a double bond, a single bond, a single bond and an epoxide bridge, or a single bond and a methylene bridge, including, where applicable, an E/Z isomer, a mixture of E/Z isomers, and/or a tautomer thereof, in each case in free form or in salt form, which process comprises I) bringing a compound of formula (II); wherein R1-R7, m, n, A, B, C, D, E and F have the same meanings as given for formula (I) above, into contact with a biocatalyst that is capable of specifically oxidising the alcohol at position 4″ in order to form a compound of formula (III), in which R1, R2, R3, R4, R5, R6, R7, m, n, A, B, C, D, E and F have the meanings given for formula (I); and 2) reacting the compound of formula (III) with an amine of the formula HN(R8)R9, wherein R8 and R9 have the same meanings as given for formula (I), and which is known, in the presence of a reducing agent.

    摘要翻译： 本发明的主题是制备式（I）化合物的方法，其中R 1 -R 9彼此独立地表示氢取代基; m为0,1或2; n为0,1,2或3; 标记为A，B，C，D，E和F的键彼此独立地表示两个相邻碳原子通过双键，单键，单键和环氧化物桥连接，或单个 键和亚甲基桥，其中包括E / Z异构体，E / Z异构体和/或其互变异构体的混合物，在任何情况下为游离形式或盐形式，该方法包括I）使 式（II）化合物; 其中R1-R7，m，n，A，B，C，D，E和F具有与上述式（I）给出的相同的含义，与能够在4'位上特异性氧化醇的生物催化剂接触， 为了形成式（III）的化合物，其中R 1，R 2，R 3，R 4，R 5，R 6，R 7，m，n，A，B，C，D，E和F具有式 （一世）; 和2）使式（III）的化合物与式HN（R8）R9的胺反应，其中R8和R9具有与式（I）给出的相同的含义，并且是已知的，在还原 代理商

    Methods for making polyketides
    2.
    发明授权
    Methods for making polyketides 有权
    聚酮化合物的制备方法

    公开(公告)号：US06551802B2

    公开(公告)日：2003-04-22

    申请号：US09735685

    申请日：2000-12-12

    申请人： Chaitan Khosla ,  Janice Lau ,  Nicola L. Pohl

    发明人： Chaitan Khosla ,  Janice Lau ,  Nicola L. Pohl

    IPC分类号： C12P1962

    CPC分类号： C07C327/30 ,  C07K2319/00 ,  C12N9/1029 ,  C12N15/52 ,  C12P19/62

    摘要： The stereochemical centers of a polyketide can be changed by replacement of ketosynthase domains in the polyketide synthase (PKS) enzyme that produces the polyketide. The specificity of the AT domains of a PKS is determined by a hypervariable region that can be replaced or altered to change the specificity of the AT domain from a naturally occurring extender unit to another naturally or non-naturally occurring extender unit. Non-naturally occurring extender units, including methylmalonyl N-acetyl cysteamine thioester can be incorporated into polyketides in recombinant host cells or in cell-free systems to make polyketides.

    摘要翻译： 聚酮化合物的立体化学中心可以通过在产生聚酮化合物的聚酮化合物合酶（PKS）酶中置换酮解酶结构域来改变。 PKS的AT结构域的特异性由可以被替换或改变的高变区确定，以将AT结构域从天然存在的延伸单元特异性改变为另一天然或非天然存在的延伸单元。 包括甲基丙二酰基N-乙酰基半胱胺硫代酯在内的非天然存在的增量单元可以掺入重组宿主细胞中的聚酮化合物或无细胞系统中以制备聚酮化合物。

    Methods for introducing hydroxyl or epoxide groups into polyketides using OleP
    4.
    发明授权
    Methods for introducing hydroxyl or epoxide groups into polyketides using OleP 失效
    使用OleP将羟基或环氧基引入聚酮化合物的方法

    公开(公告)号：US06828126B2

    公开(公告)日：2004-12-07

    申请号：US09991448

    申请日：2001-11-16

    申请人： Robert McDaniel

    发明人： Robert McDaniel

    IPC分类号： C12P1962

    CPC分类号： C12N15/52 ,  C12P19/62

    摘要： The heterologous expression of the oleandomycin polyketide synthase (OlePKS) in Streptomyces lividans, produces 8,8 a-deoxyoleandolide, an aglycone precursor of oleandomycin. The co-expression with deoxyerythronolide B synthase (DEBS) in S. lividans of the P450 monooxygenase OleP produces 8,8 a-dihydroxy-6-deoxyerythonolide B and other derivatives that are precursors to important macrolide antibiotics.

    摘要翻译： 木兰霉素聚酮化合物合酶（OlePKS）在链霉菌（Streptomyces lividans）中的异源表达产生8,8α-脱氧山ol ide苷，即肉豆蔻霉素的糖苷配基前体。 与脱氧红霉素B合酶（DEBS）在P450单加氧酶OleP的变性链中的共表达产生8,8α-二羟基-6-脱氧山梨醇苷B和作为重要大环内酯类抗生素前体的其它衍生物。

    Recombinant host cells for the production of polyketides
    10.
    发明授权
    Recombinant host cells for the production of polyketides 有权
    用于生产聚酮化合物的重组宿主细胞

    公开(公告)号：US06177262B1

    公开(公告)日：2001-01-23

    申请号：US09181833

    申请日：1998-10-28

    申请人： Rainer Ziermann ,  Mary C. Betlach

    发明人： Rainer Ziermann ,  Mary C. Betlach

    IPC分类号： C12P1962

    CPC分类号： C12P19/62 ,  C12N9/00

    摘要： Yields of polyketides produced in host cells such as Streptomyces can be increased by coexpression of the ptpA gene. The introduction of recombinant vectors encoding ptpA and polyketide synthase genes is more efficient and does not require methyl-free DNA if the host cell is a restriction/methylation deficient strain, such as Streptomyces lividans K4-114, K4-155, or K27-39.

    摘要翻译： 可以通过ptpA基因的共表达来增加在宿主细胞如链霉菌中产生的聚酮化合物的产量。 编码ptpA和聚酮化合物合酶基因的重组载体的引入更有效，并且如果宿主细胞是限制性/甲基化缺陷型菌株，例如变形链霉菌K4-114，K4-155或K27-39，则不需要无甲基DNA 。