The biosynthesis of the aromatic myxobacterial electron transport inhibitor stigmatellin is directed by a novel type of modular polyketide synthase
The biosynthesis of the aromatic myxobacterial electron transport inhibitor stigmatellin is directed by a novel type of modular polyketide synthase
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DOI：
10.1074/jbc.m111738200
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发表时间：
2002-04-12
影响因子：
4.8
通讯作者：
Müller, R
中科院分区：
文献类型：
--
作者：
Gaitatzis, N;Silakowski, B;Müller, R
报道了65000 bp的柱头蛋白生物合成基因簇的分子分析推论。生物合成基因（stiA-J）编码一种不寻常的细菌模块化I型聚酮合成酶（PKS），负责形成这种芳香电子传递抑制剂，这种抑制剂是由金头粘杆菌产生的。PKS基因簇参与柱头蛋白的生物合成显示使用定点诱变。PKS的一个模块被认为是在生物合成过程中迭代使用的，这似乎涉及一个不寻常的生物合成中间体的转酰基化，从酰基载体蛋白结构域回到之前的酮合酶结构域。最后，聚酮链被环化和芳香化，这可能是由StiJ中一个新的c端结构域催化的，它不像硫酯酶。饲养试验结果与提出的生物合成方案吻合较好。与迄今为止报道的所有其他PKS I型系统相比，StiA-J的每个模块都编码在一个单独的基因上。该基因簇包含一个“独立的”o -甲基转移酶和两个嵌入在PKS中的不寻常的o -甲基转移酶结构域。此外，参与pks后芳香环羟基化的细胞色素P450单加氧酶编码基因失活导致两种新的柱头蛋白衍生物的形成。
Deductions from the molecular analysis of the 65,000-bp stigmatellin biosynthetic gene cluster are reported. The biosynthetic genes (stiA-J) encode an unusual bacterial modular type I polyketide synthase (PKS) responsible for the formation of this aromatic electron transport inhibitor produced by the myxobacterium Stigmatella aurantiaca. Involvement of the PKS gene cluster in stigmatellin biosynthesis is shown using site-directed mutagenesis. One module of the PKS is assumed to be used iteratively during the biosynthetic process, which seems to involve an unusual transacylation of the biosynthetic intermediate from an acyl carrier protein domain back to the preceding ketosynthase domain. Finally, the polyketide chain which is presumably catalyzed by a novel C-terminal domain in StiJ that does not resemble thioesterases, is cyclized and aromatized. The presented results of feeding experiments are in good agreement with the proposed biosynthetic scheme. In contrast to all other PKS type I systems reported to date, each module of StiA-J is encoded on a separate gene. The gene cluster contains a "stand alone" O-methyltransferase and two unusual O-methyltransferase domains embedded in the PKS. In addition, inactivation of a cytochrome P450 monooxygenase-encoding gene involved in post-PKS hydroxylation of the aromatic ring leads to the formation of two novel stigmatellin derivatives.