Synergistic actions of a monooxygenase and cyclases in aromatic polyketide biosynthesis
Synergistic actions of a monooxygenase and cyclases in aromatic polyketide biosynthesis
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DOI：
10.1002/cbic.200800178
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发表时间：
2008-07-21
期刊：
影响因子：
3.2
通讯作者：
Tang, Yi
中科院分区：
文献类型：
--
作者：
Zhan, Jixun;Watanabe, Kenji;Tang, Yi
II 型聚酮化合物合酶 (PKS) 是负责细菌芳香族聚酮化合物生物合成的酶。[1, 2] II 型最小 PKS — 由 β-酮脂酰合酶 (KSα)、链长因子（CLF 或 KSβ）和酰基载体蛋白 (ACP) 组成 — 通过连续的克莱森式脱羧缩合合成新生聚酮化合物链。然后，新生的聚酮化合物链分别在专用酮还原酶（KR）和环化酶的催化下进行区域选择性还原和环化，产生芳香苷元。一般来说，这些直接剪裁酶作为 ACHTUNGTRENNUNG 独立蛋白质发挥作用，这一特征促进了 KR 和环化酶的异源组合用于新聚酮化合物的生物合成。[3]Pradimicin A（方案 1）是一种由 Actinomadura hibisca P157–2 生物合成的芳香族聚酮化合物。[4]它含有一个二氢苯并[α]并四苯醌核心，通过五次区域选择性环化衍生自十二烷基肽骨架。聚酮化合物在环E处的羧基端被D-丙氨酸酰胺化，而非芳香环D被由D-吡喃木糖和4-甲基氨基-4-脱-组成的二糖取代。
Type II polyketide synthases (PKSs) are enzymes responsible for the biosynthesis of bacterial aromatic polyketides.[1, 2] The type II minimum PKS—which consists of the β-ketoacyl synthase (KSα), chain length factor (CLF or KSβ), and acyl carrier protein (ACP)—synthesizes the nascent polyketide chain by successive Claisen-like decarboxylative condensations. The nascent polyketide chain is then subjected to regioselective reduction and cyclization catalyzed by dedicated ketoreductases (KRs) and cyclases, respectively, to yield an aromatic aglycon. In general, these immediate tailoring enzymes function as ACHTUNGTRENNUNGindependent proteins, a feature that has facilitated the use of heterologous combinations of KRs and cyclases for the biosynthesis of new polyketides.[3]Pradimicin A (Scheme 1) is an aromatic polyketide biosynthesized by Actinomadura hibisca P157–2.[4] It contains a dihydrobenzo [α] naphthacenequinone core, derived from a dodecaketide backbone through five regioselective cyclizations. The carboxyl end of the polyketide at ring E is amidated with D-alanine, while the nonaromatic ring D is substituted with a disaccharide consisting of D-xylopyranose and 4-methylamino-4-de-