Macrotetrolide biosynthesis: a novel type II polyketide synthase.
Macrotetrolide biosynthesis: a novel type II polyketide synthase.
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DOI：
10.1002/tcr.10042
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发表时间：
2002-11
期刊：
影响因子：
6.6
通讯作者：
B. Shen;H. Kwon
中科院分区：
文献类型：
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作者：
B. Shen;H. Kwon
聚酮合成是由聚酮合成酶（PKS）催化的，目前已知三种类型的细菌PKS。用同位素标记前体的加料实验确定了大四烷内酯的聚酮来源，但标记模式不能根据已建立的PKS范式进行合理化。对大四萜内酯生物合成过程的遗传分析揭示了一个前所未有的聚酮基因集群，该集群具有编码离散酮酰合成酶（KS）的5个基因和编码离散酮酰还原酶（KR）的4个基因，但缺乏酰基载体蛋白（ACP）。大四环素内酯的生物合成涉及一种新型II型PKS，它直接作用于酰基辅酶a底物，非迭代地起作用，并催化C-C和C-O键的形成。这些发现再次证明了大自然在制造复杂分子方面的多功能性，并为PKS工程提供了新的策略，以进一步扩大聚酮库的范围和多样性。它们也将为寻找具有新化学性质的PKS用于组合生物合成提供启示。
Polyketide biosynthesis is catalyzed by polyketide synthase (PKS) and three types of bacterial PKS are known to date. Feeding experiments with isotope-labeled precursors established the polyketide origin of the macrotetrolides, but the labeling pattern cannot be rationalized according to the established PKS paradigm. Genetic analysis of the macrotetrolide biosynthesis unveiled an unprecedented organization for a polyketide gene cluster that features five genes encoding discrete ketoacyl synthase (KS) and four genes encoding discrete ketoreductase (KR) but lacking an acyl carrier protein (ACP). Macrotetrolide biosynthesis is proposed to involve a novel type II PKS that acts directly on acyl CoA substrates, functions noniteratively, and catalyzes both C-C and C-O bond formation. These findings demonstrate once again Nature's versatility in making complex molecules and suggests new strategies for PKS engineering to further expand the scope and diversity of polyketide library. They also should serve as an inspiration in searching for PKS with novel chemistry for combinatorial biosynthesis.