公开(公告)号：US5250435A

公开(公告)日：1993-10-05

申请号：US709950

申请日：1991-06-04

申请人： William H. Cover ,  Rebecca L. Dabora ,  Anderson Hong ,  Christopher Reeves ,  Robert W. Stieber ,  Victor A. Vinci

发明人： William H. Cover ,  Rebecca L. Dabora ,  Anderson Hong ,  Christopher Reeves ,  Robert W. Stieber ,  Victor A. Vinci

IPC分类号： C12P7/24 ,  C07C59/11 ,  C12N1/14 ,  C12P7/42 ,  C12P17/06 ,  C12R1/66 ,  C07D305/00

CPC分类号： C12R1/66 ,  C12P17/06 ,  C12P7/42 ,  Y10S435/913

摘要： Novel strains of Aspergillus terreus have been discovered which provide fermentation production of at least 5.2 g/L of 7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-hydroxy-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid (triol acid, I), but with production of not more than 0.85 g/L of (triol acid)-related side products and specifically less than 0.10 mg/liter of lovastatin. The predominant fermentation product triol acid, may be converted in a straightforward manner to its lactone form, in which it is an inhibitor of HMG-CoA reductase and thus useful as an antihypercholesterolemic agent, and in which it may also serve as an intermediate for preparation of other HMG-CoA reductase inhibitors.

公开(公告)号：US06312931B1

公开(公告)日：2001-11-06

申请号：US09502910

申请日：2000-02-11

申请人： Mary O'Dwyer ,  William H. Cover ,  Jeffrey M. Boeger ,  Karen A. Rieger

发明人： Mary O'Dwyer ,  William H. Cover ,  Jeffrey M. Boeger ,  Karen A. Rieger

IPC分类号： C12N1300

CPC分类号： A61L2/0011 ,  C12N9/96

摘要： A method of protecting a biomolecule from substantial degradation while reducing the content of a pathogen or chemical toxin contained by a biologically derived composition is described. The method involves first providing a biologically derived composition containing a pathogen or chemical toxin and at least one biologically active molecule. Then, adding albumin to the composition to create a supplemented composition. Next, subjecting the supplemented composition to polychromatic pulsed light to degrade the pathogen or toxin. The polychromatic light includes at least one high-intensity, short duration pulse of incoherent polychromatic light in a broad spectrum. The light intensity is at least about 0.01 J/cm2, the pulse duration is 10 ns to 100 ms and the light wavelengths are between about 170 nm and about 2600 nm. The content of the albumin in the supplemented composition is such that the subjecting step reduces the content of the pathogen or chemical toxin by at least a factor of 10 without degrading the biological activity of the biomolecule to an unacceptable level. Finally, the biomolecule is recovered in a biologically active state.

摘要翻译： 描述了一种保护生物分子免受实质降解同时降低生物衍生组合物含有的病原体或化学毒素含量的方法。 该方法首先提供含有病原体或化学毒素和至少一种生物活性分子的生物衍生的组合物。 然后，向组合物中加入白蛋白以产生补充的组合物。 接下来，将补充的组合物进行多色脉冲光降解病原体或毒素。 多色光包括广谱中至少一个高强度，短持续脉冲的非相干多色光。 光强度为至少约0.01J / cm 2，脉冲持续时间为10ns至100ms，光波长在约170nm至约2600nm之间。 补充组合物中白蛋白的含量使得经受步骤将病原体或化学毒素的含量降低至少10倍，而不会降低生物分子的生物活性至不可接受的水平。 最后，生物分子在生物活性状态下回收。

公开(公告)号：US5223415A

公开(公告)日：1993-06-29

申请号：US832545

申请日：1992-02-07

申请人： Michael J. Conder ,  Steven J. Cianciosi ,  William H. Cover ,  Rebecca L. Dabora ,  Eric T. Pisk ,  Robert W. Stieber ,  Bogdan Tehlewitz ,  Gregory L. Tewalt

发明人： Michael J. Conder ,  Steven J. Cianciosi ,  William H. Cover ,  Rebecca L. Dabora ,  Eric T. Pisk ,  Robert W. Stieber ,  Bogdan Tehlewitz ,  Gregory L. Tewalt

IPC分类号： C07C59/46 ,  C12P7/42 ,  C12P17/06 ,  C12R1/645 ,  C12R1/66 ,  C12R1/77 ,  C12R1/78 ,  C12R1/785 ,  C12R1/88

CPC分类号： C12P17/06 ,  C07C59/46 ,  C12P7/42

摘要： Biosynthetic production of 7-[1',2',6',-7',8',8a'(R)-hexahydro-2'(S),6'(R)-dimethyl-8'(S)-hydroxy-1'(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid, "triol acid", is accomplished by enzymatic hydrolysis of lovastatin acid or a salt thereof, by treating it with Clonostachys compactiuscula ATCC 38009 or ATCC 74178, or mutants thereof, or a cell-free extract derived therefrom, or a hydrolase derived therefrom. The triol acid and its lactone form are both inhibitors of HMG-CoA reductase and thus useful as anti-hypercholesterolemic agents, and may also serve as intermediates for preparation of other HMG-CoA reductase inhibitors. Also, in the synthesis of simvastatin by direct methylation of lovastatin, selective hydrolysis of residual lovastatin salt by treatment with Clonostachys compactiuscula ATCC 38009 or ATCC 74178 or mutants thereof or a cell-free extract derived therefrom, or a hydrolase derived therefrom yields the "triol" salt which can be easily separated from simvastatin.

摘要翻译： 7- [1'，2'，6'，-7'，8'，8a'（R） - 六氢-2'（S），6'（R） - 二甲基-8'（S） - 羟基-1'（S） - 萘基] -3（R），5（R） - 二羟基庚酸，“三醇酸”是通过洛伐他汀酸或其盐的酶水解，通过用克隆氏菌（Clonostachys compactiuscula）ATCC 38009 或ATCC 74178，或其突变体，或由其衍生的无细胞提取物或由其衍生的水解酶。 三醇酸及其内酯形式均为HMG-CoA还原酶的抑制剂，因此可用作抗高胆固醇血症药，也可用作制备其他HMG-CoA还原酶抑制剂的中间体。 此外，在通过洛伐他汀的直接甲基化合成辛伐他汀的情况下，通过用克隆氏菌（Clonostachys compactiuscula）ATCC 38009或ATCC 74178或其突变体或由其衍生的无细胞提取物或其衍生的水解酶进行选择性水解残留的洛伐他汀盐，得到“三醇 “盐可以很容易地与辛伐他汀分离。