恶臭假单胞菌M10对镇痛剂氢吗啡酮（吗啡代谢中间体）的生物合成。
Biological synthesis of the analgesic hydromorphone, an intermediate in the metabolism of morphine, by Pseudomonas putida M10.
作者信息
Hailes A M, Bruce N C
机构信息
Institute of Biotechnology, University of Cambridge, United Kingdom.
出版信息
Appl Environ Microbiol. 1993 Jul;59(7):2166-70. doi: 10.1128/aem.59.7.2166-2170.1993.
Abstract
The morphine alkaloid hydromorphone (dihydromorphinone) was identified as an intermediary metabolite in the degradation of morphine by Pseudomonas putida M10. A constitutive NADH-dependent morphinone reductase capable of catalyzing the reduction of the 7,8-unsaturated bond of morphinone and codeinone, yielding hydromorphone and hydrocodone, respectively, was shown to be present in cell extracts. The structures have been identified by 1H nuclear magnetic resonance and mass spectrometry. Morphinone reductase has been partially purified by anion-exchange and gel filtration chromatography. This enzyme has potential applications as a biocatalyst for the synthesis of the highly potent analgesic hydromorphone and the antitussive hydrocodone.
摘要
吗啡生物碱氢吗啡酮（二氢吗啡酮）被鉴定为恶臭假单胞菌M10降解吗啡过程中的一种中间代谢产物。细胞提取物中存在一种组成型的依赖烟酰胺腺嘌呤二核苷酸（NADH）的吗啡酮还原酶，它能够催化吗啡酮和可待因酮的7,8-不饱和键的还原反应，分别生成氢吗啡酮和氢可酮。其结构已通过氢核磁共振（1H NMR）和质谱分析得以鉴定。吗啡酮还原酶已通过阴离子交换和凝胶过滤色谱法进行了部分纯化。这种酶作为生物催化剂在合成高效镇痛药氢吗啡酮和镇咳药氢可酮方面具有潜在应用价值。
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本文引用的文献
1
[Studies in the field of microbiological decomposition. XVII. Transformation of alkaloids in the morphine series by Trametes sanguinea. (2)].[微生物分解领域的研究。十七。血红栓菌对吗啡系列生物碱的转化。(2)]
Chem Pharm Bull (Tokyo). 1962 Oct;10:981-4.
2
[Studies in the field of microbiological decomposition. XVI. Decomposition of alkaloids of the morphine group by Trametes sanguinea].[微生物分解领域的研究。十六。血红栓菌对吗啡类生物碱的分解]
Chem Pharm Bull (Tokyo). 1962 Jan;10:67-70. doi: 10.1248/cpb.10.67.
3
Identification of transformation products arising from bacterial oxidation of codeine by Streptomyces griseus.由灰色链霉菌对可待因进行细菌氧化产生的转化产物的鉴定。
Appl Environ Microbiol. 1985 Oct;50(4):831-6. doi: 10.1128/aem.50.4.831-836.1985.
4
Microbial degradation of the morphine alkaloids. Purification and characterization of morphine dehydrogenase from Pseudomonas putida M10.吗啡生物碱的微生物降解。恶臭假单胞菌M10中吗啡脱氢酶的纯化与特性分析。
Biochem J. 1991 Mar 15;274 ( Pt 3)(Pt 3):875-80. doi: 10.1042/bj2740875.
5
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6
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Anal Biochem. 1976 May 7;72:248-54. doi: 10.1016/0003-2697(76)90527-3.
7
Transformation of morphine by resting cells and cell-free systems of Arthrobacter sp.节杆菌静止细胞和无细胞体系对吗啡的转化
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8
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J Chromatogr. 1979 Apr 1;171:371-6. doi: 10.1016/s0021-9673(01)95317-8.
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