cis-Delta(2,3)-double bond of phoslactomycins is generated by a post-PKS tailoring enzyme.
cis-Delta(2,3)-double bond of phoslactomycins is generated by a post-PKS tailoring enzyme.
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DOI：
10.1021/ja8044162
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发表时间：
2008-09-17
影响因子：
15
通讯作者：
Reynolds, Kevin A.
中科院分区：
文献类型：
--
作者：
Palaniappan, Nadaraj;Alhamadsheh, Mamoun M.;Reynolds, Kevin A.
由链霉菌HK 803产生的抗真菌磷霉素（PLM A-F）在结构上是不寻常的，因为它们的四个双键中有三个是顺式形式（Δ 12，13，Δ 14，15，Δ 2，3）。PLM聚酮合酶（PKS）在模块1、2和5中具有预测的脱水酶催化结构域，该结构域是建立其中两个顺式双键（Δ 1,2，13 Δ 14，15）以及唯一的反式Δ6，7双键所需的。相比之下，PLM的不饱和内酯部分中的顺式Δ 2，3的形成呈现出一个谜，因为在模块7中不存在预测的脱氢酶结构域。在本文中，我们已经证明，与PKS脱氢酶结构域没有同源性的plmT 2基因产物是有效形成顺式Δ 2，3烯烃所需的。在plmT 2缺失突变体中制备了一系列新的PLM产物，其中保留了C3羟基。然而，在所有这些情况下，羟基基团被丙二酸酯化。这些丙二酰化PLM产物通过简单的碱催化脱羧消除反应转化为相应的顺式Δ 2，3 PLM产物和乙酸。plmT 2缺失突变体中天然PLM产生的完全或部分恢复可分别通过基于质粒的plmT 2或fos ORF 4（来自fostriecin生物合成基因簇的同源基因）表达来实现。这些数据表明，在其他PKS途径的不饱和6元内酯部分的建立，也起作用，并提供了第一个生物合成的见解可能的途径，其中不寻常的丙二酰化聚酮产品的产生。
The antifungal phoslactomycins (PLM A-F), produced by Streptomyes sp HK803, are structurally unusual in that three of their four double bonds are in the cis form (Δ12,13, Δ14,15, Δ2,3). The PLM polyketide synthase (PKS) has the predicted dehydratase catalytic domain in modules 1,2 and 5 required for establishing two of these cis double bonds (Δ12,13Δ14,15), as well as the only trans Δ6,7double bond. By contrast, the formation of the cis Δ2,3 in the unsaturated lactone moiety of PLMs has presented an enigma because the predicted dehydratase domain in module 7 is absent. Herein, we have demonstrated that the plmT2 gene product, with no homology to PKS dehydratase domains, is required for efficient formation of the cis Δ2,3 alkene. A series of new PLM products in which the C3 hydroxyl group is retained, are made in plmT2 deletion mutants. In all of these cases, however, the hydroxyl group is esterified with malonic acid. These malonylated PLM products are converted to the corresponding cis Δ2,3 PLM products and acetic acid by a facile base-catalyzed decarboxylative elimination reaction. Complete or partial restoration of natural PLM production in a plmT2 deletion mutant can be accomplished by plasmid based expression of plmT2 or fos ORF4 (a homologous gene from the fostriecin biosynthetic gene cluster), respectively. The data indicate that dehydratase-independent pathways also function in establishment of unsaturated 6-membered lactone moieties in other PKS pathways, and provide the first biosynthetic insights into the possible routes by which unusual malonylated polyketide products are generated.
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影响因子：
2.9
作者：
Kim, BS;Cropp, TA;Reynolds, KA
通讯作者：
Reynolds, KA
影响因子：
3.2
作者：
Caffrey, P
通讯作者：
Caffrey, P
影响因子：
4.8
作者：
Palaniaappan, N;Kim, BS;Reynolds, KA
通讯作者：
Reynolds, KA
DOI：
10.1007/s10295-006-0116-1
发表时间：
2006-07-01
影响因子：
3.4
作者：
Ghatge, Mohini;Palaniappan, Nadaraj;Reynolds, Kevin
通讯作者：
Reynolds, Kevin
影响因子：
3.3
作者：
Hu, ZH;Reid, R;Gramajo, H
通讯作者：
Gramajo, H