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首页> 外文期刊>Biotechnology Advances: An International Review Journal >Progress on molecular breeding and metabolic engineering of biosynthesis pathways of C(30), C(35), C(40), C(45), C(50) carotenoids
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Progress on molecular breeding and metabolic engineering of biosynthesis pathways of C(30), C(35), C(40), C(45), C(50) carotenoids

机译：C（30），C（35），C（40），C（45），C（50）类胡萝卜素的生物合成途径的分子育种和代谢工程研究进展

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At least 700 natural carotenoids have been characterized; they can be classified into C(30), C(40) and C(50) subfamilies. The first step of C(40) pathway is the combination of two molecules of geranylgeranyl pyrophosphate to synthesize phytoene by phytoene synthase (CrtB or PSY). Most natural carotenoids originate from different types and levels of desaturation by phytoene desaturase (CrtI or PDS+ZDS), cyclization by lycopene cyclase (CrtY or LYC) and other modifications by different modifying enzyme (CrtA, CrtU, CrtZ or BCH, CrtX, CrtO, etc.) of this C(40) backbone. The first step of C(30) pathway is the combination of two molecules of FDP to synthesize diapophytoene by diapophytoene synthase (CrtM). But natural C(30) pathway only goes through a few steps of desaturation to form diaponeurosporene by diapophytoene desaturase (CrtN). Natural C(50) carotenoid decaprenoxanthin is synthesized starting from the C(40) carotenoid lycopene by the addition of 2 C(5) units. Concerned the importance of carotenoids, more and more attention has been concentrated on achieving novel carotenoids. The method being used successfully is to construct carotenoids biosynthesis pathways by metabolic engineering. The strategy of metabolic engineering is to engineer a small number of stringent upstream enzymes (CrtB, CrtI, CrtY, CrtM, or CrtN), then use a lot of promiscuous downstream enzymes to obtain large number of novel carotenoids. Two key enzymes phytoene desaturase (CrtI(m)) and lycopene cyclase (CrtY(m)) have been modified and used with a series of downstream modifying enzymes with broad substrate specificity, such as monooxygenase (CrtA), carotene desaturase (CrtU), carotene hydroxylase (CrtZ), zeaxanthin glycosylase (CrtX) and carotene ketolase (CrtO) to extend successfully natural C(30) and C(40) pathways in E. coli. Existing C(30) synthase CrtM to synthesize carotenoids with different chain length have been engineered and a series of novel carotenoids have been achieved using downstream modifying enzymes. C(35) carotenoid biosynthesis pathway has been constructed in E. coli as described. C(45) and C(50) carotenoid biosynthesis pathways have also been constructed in E. coli, but it is still necessary to extend these two pathways. Those novel acyclic or cyclic carotenoids have a potential ability to protect against photooxidation and radical-mediated peroxidation reactions which makes them interesting pharmaceutical candidates.
机译：至少已鉴定出700种天然类胡萝卜素。它们可以分为C（30），C（40）和C（50）子家族。 C（40）途径的第一步是将两个分子的香叶基香叶基焦磷酸酯结合起来，通过八氢番茄红素合酶（CrtB或PSY）合成八氢番茄红素。大多数天然类胡萝卜素源自不同类型和水平的八氢番茄红素去饱和酶（CrtI或PDS + ZDS），番茄红素环化酶（CrtY或LYC）的环化作用以及其他修饰酶（CrtA，CrtU，CrtZ或BCH，CrtX，CrtO）的修饰等C）（40）主干。 C（30）途径的第一步是将FDP的两个分子结合起来，通过二po并ene合酶（CrtM）合成并po。但是自然的C（30）途径仅通过去饱和二烯脱饱和酶（CrtN）的几个去饱和步骤而形成二萘并戊二烯。从C（40）类胡萝卜素番茄红素开始，通过添加2个C（5）单元，可以合成天然C（50）类胡萝卜素癸酸黄嘌呤。关于类胡萝卜素的重要性，越来越多的注意力集中在获得新型类胡萝卜素上。成功使用的方法是通过代谢工程构建类胡萝卜素的生物合成途径。代谢工程的策略是工程化少量严格的上游酶（CrtB，CrtI，CrtY，CrtM或CrtN），然后使用大量混杂的下游酶来获得大量新的类胡萝卜素。修饰了两个关键的酶八氢番茄红素去饱和酶（CrtI（m））和番茄红素环化酶（CrtY（m）），并与一系列具有广泛底物特异性的下游修饰酶一起使用，例如单加氧酶（CrtA），胡萝卜素去饱和酶（CrtU），胡萝卜素羟化酶（CrtZ），玉米黄质糖基化酶（CrtX）和胡萝卜素酮醇酶（CrtO）成功地扩展了大肠杆菌中的天然C（30）和C（40）途径。现有的C（30）合酶CrtM可以合成具有不同链长的类胡萝卜素，并且已经使用下游修饰酶实现了一系列新型类胡萝卜素。如上所述，已在大肠杆菌中构建了C（35）类胡萝卜素生物合成途径。 C（45）和C（50）类胡萝卜素生物合成途径也已在大肠杆菌中构建，但仍然有必要扩展这两个途径。那些新颖的无环或环状类胡萝卜素具有潜在的保护能力，可防止光氧化和自由基介导的过氧化反应，这使它们成为有趣的药物候选物。

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