Environmental control of the calicheamicin polyketide synthase leads to detection of a programmed octaketide and a proposal for enediyne biosynthesis.
Environmental control of the calicheamicin polyketide synthase leads to detection of a programmed octaketide and a proposal for enediyne biosynthesis.
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DOI：
10.1002/anie.201206462
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发表时间：
2012-11-05
影响因子：
16.6
通讯作者：
Townsend, Craig A.
中科院分区：
文献类型：
--
作者：
Belecki, Katherine;Townsend, Craig A.
烯二炔天然产物除了显示出作为合成挑战和生物合成之谜都相当显著的结构特征之外，还显示出有效的抗肿瘤和抗生素活性。[1]该组的成员通常包含设计用于DNA识别的结构组分和含有侧接三键的烯烃（或掩蔽的烯烃）的碳环核心。正如经典的同位素标记研究所预示的那样，[2] 9元和10元烯二炔亚类的生物合成基因簇序列证实了烯二炔核心结构的碳骨架是由I型迭代聚酮酶（PKS）家族在自然界中形成的。[3]这些多功能酶利用单组结构域催化活化丙二酰单元的重复缩合和程序化还原加工，类似于哺乳动物脂肪酸合成。然而，在聚酮化合物生物合成中，每轮两碳延伸的加工程度由PKS控制，允许酮、羟基和双键保留在生长的聚酮化合物链中。中间体在整个链延伸过程中保持共价连接到PKS，使这些编程事件的调查复杂化。[4]此外，在迭代系统中重复使用单组结构域通常使得难以预测直接PKS产物，特别是如果它在最终天然产物的途中被高度修饰。
The enediyne natural products exhibit potent antitumor and antibiotic activity in addition to displaying structural features that are quite remarkable both as a synthetic challenge and a biosynthetic enigma.[1] Members of this group typically incorporate a structural component designed for DNA recognition and a carbocyclic core containing an alkene (or masked alkene) flanked by triple bonds. It is this enediyne moiety that gives this class of compounds their name and their potent activity.As was foreshadowed by classical isotopic labeling studies,[2] biosynthetic gene cluster sequences for both 9-and 10-membered subclasses of enediynes confirm that the carbon skeletons of the enediyne core structures are made in nature by a family of type I iterative polyketide synthases (PKSs).[3] These multifunctional enzymes utilize a single set of domains to catalyze the repeated condensation and programmed reductive processing of activated malonyl units, analogous to mammalian fatty acid synthesis. In polyketide biosynthesis, however, the extent of processing in each round of two-carbon extension is controlled by the PKS, allowing for retention of ketones, hydroxyl groups, and double bonds into the growing polyketide chain. Intermediates remain covalently tethered to the PKS throughout the chain elongation process, complicating the investigation of these programming events.[4] Furthermore, the repeated use of a single set of domains in iterative systems often makes it difficult to predict the direct PKS product, particularly if it is highly modified en route to the final natural product.
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影响因子：
15
作者：
TOKIWA, Y;MIYOSHISAITOH, M;IWASAKI, S
通讯作者：
IWASAKI, S
影响因子：
15
作者：
Vagstad, Anna L.;Bumpus, Stefanie B.;Belecki, Katherine;Kelleher, Neil L.;Townsend, Craig A.
通讯作者：
Townsend, Craig A.
影响因子：
15
作者：
HENSENS, OD;GINER, JL;GOLDBERG, IH
通讯作者：
GOLDBERG, IH
DOI：
10.1073/pnas.0711625105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Zhang, Jian;Van Lanen, Steven G.;Shen, Ben
通讯作者：
Shen, Ben
影响因子：
56.9
作者：
Liu, W;Christenson, SD;Shen, B
通讯作者：
Shen, B