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一种工业适用的平台,可将蒂巴因生物转化为奥列巴因和可待因转化为吗啡。

An industrially applicable platform for bioconversion of thebaine to oripavine and codeine to morphine.

机构信息

The Department of Chemical Engineering and the Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, 3010, Australia.

Sun Pharmaceutical Industries Australia Pty Ltd., Princes Highway, Port Fairy, Victoria 3281, Australia.

出版信息

Chem Commun (Camb). 2023 May 18;59(41):6251-6254. doi: 10.1039/d3cc00534h.

DOI:10.1039/d3cc00534h
PMID:37132502
Abstract

A whole cell biotransformation platform converting thebaine to oripavine and codeine to morphine was demonstrated with industrially applicable yields (∼1.2 × 10 g L h or ∼1.2 × 10 g L h), improving >13 400-fold upon morphine production in yeast. Mutations enhanced enzyme performance and the use of a purified substrate with rich raw poppy extract expanded applicability.

摘要

利用工业上可行的产率(约 1.2×10 g L h 或约 1.2×10 g L h),展示了一种全细胞生物转化平台,可将蒂巴因转化为异土木防己碱和可待因转化为吗啡,相比于酵母中生产吗啡,提高了>13400 倍。突变增强了酶的性能,而使用富含罂粟原料提取物的纯化底物则扩大了其适用性。

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An industrially applicable platform for bioconversion of thebaine to oripavine and codeine to morphine.一种工业适用的平台,可将蒂巴因生物转化为奥列巴因和可待因转化为吗啡。
Chem Commun (Camb). 2023 May 18;59(41):6251-6254. doi: 10.1039/d3cc00534h.
2
Transformation of thebaine to oripavine, codeine, and morphine by rat liver, kidney, and brain microsomes.大鼠肝脏、肾脏和脑微粒体将蒂巴因转化为羟考酮、可待因和吗啡的过程。
Proc Natl Acad Sci U S A. 1988 Feb;85(4):1267-71. doi: 10.1073/pnas.85.4.1267.
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Synthesis of thebaine and oripavine from codeine and morphine.由可待因和吗啡合成蒂巴因和阿片碱。
J Med Chem. 1975 Nov;18(11):1074-7. doi: 10.1021/jm00245a006.
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Analgesia: morphine-pathway block in top1 poppies.镇痛作用:top1罂粟中吗啡途径的阻断
Nature. 2004 Sep 23;431(7007):413-4. doi: 10.1038/431413a.
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Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli.利用工程化大肠杆菌通过逐步发酵进行阿片类药物的全生物合成。
Nat Commun. 2016 Feb 5;7:10390. doi: 10.1038/ncomms10390.
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Thebaine O-demethylation to oripavine: genetic differences between two rat strains.蒂巴因O-去甲基化生成阿片碱:两种大鼠品系之间的遗传差异。
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Quantification of Morphine, Codeine, and Thebaine in Home-Brewed Poppy Seed Tea by LC-MS/MS.采用液相色谱-串联质谱法对自酿罂粟籽茶中的吗啡、可待因和蒂巴因进行定量分析。
J Forensic Sci. 2018 Jul;63(4):1229-1235. doi: 10.1111/1556-4029.13664. Epub 2017 Oct 3.

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