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利用角鲨烯合酶构建类胡萝卜素生物合成途径。

Construction of carotenoid biosynthetic pathways using squalene synthase.

机构信息

Department of Applied Chemistry and Biotechnology, Chiba University, 1-33, Yayoi-cho, Inage, Chiba 263-8522, Japan.

Department of Applied Chemistry and Biotechnology, Chiba University, 1-33, Yayoi-cho, Inage, Chiba 263-8522, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.

出版信息

FEBS Lett. 2014 Jan 31;588(3):436-42. doi: 10.1016/j.febslet.2013.12.003. Epub 2013 Dec 10.

Abstract

The first committed steps of steroid/hopanoid pathways involve squalene synthase (SQS). Here, we report the Escherichia coli production of diaponeurosporene and diapolycopene, yellow C30 carotenoid pigments, by expressing human SQS and Staphylococcus aureus dehydrosqualene (C30 carotenoid) desaturase (CrtN). We suggest that the carotenoid pigments are synthesized mainly via the desaturation of squalene rather than the direct synthesis of dehydrosqualene through the non-reductive condensation of prenyl diphosphate precursors, indicating the possible existence of a "squalene route" and a "lycopersene route" for C30 and C40 carotenoids, respectively. Additionally, this finding yields a new method of colorimetric screening for the cellular activity of squalene synthases, which are major targets for cholesterol-lowering drugs.

摘要

甾醇/三萜类化合物途径的第一步涉及鲨烯合酶(SQS)。在这里,我们通过表达人源 SQS 和金黄色葡萄球菌脱鲨烯(C30 类胡萝卜素)脱氢酶(CrtN),报告了大肠杆菌中迪波内诺孢烯和迪波里考派烯(黄色 C30 类胡萝卜素)的生产。我们认为,类胡萝卜素色素主要通过鲨烯的去饱和作用合成,而不是通过前体二磷酸香叶基香叶基的非还原缩合直接合成脱鲨烯,这表明可能存在 C30 和 C40 类胡萝卜素的“鲨烯途径”和“番茄红素途径”。此外,这一发现为鲨烯合酶的细胞活性提供了一种新的比色筛选方法,鲨烯合酶是降胆固醇药物的主要靶标。

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