Sequence, cloning, and analysis of the fluvirucin B1 polyketide synthase from Actinomadura vulgaris.
Sequence, cloning, and analysis of the fluvirucin B1 polyketide synthase from Actinomadura vulgaris.
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DOI：
10.1021/sb4000355
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发表时间：
2013-11-15
影响因子：
4.7
通讯作者：
Schnarr, Nathan A.
中科院分区：
文献类型：
--
作者：
Lin, Tsung-Yi;Borketey, Lawrence S.;Prasad, Gitanjeli;Waters, Stephanie A.;Schnarr, Nathan A.
流感病毒素B1由普通放线菌产生，是一种由14个成员组成的大内酰胺类化合物，对多种感染性真菌和甲型流感都有活性。尽管合成界对此很感兴趣，但关于其生物合成来源的信息很少。在此，我们报道了流感病毒B1聚酮合成酶及其相关酶的鉴定和初步性质。该簇由5个延伸模块组成，两侧是N-端酰基载体蛋白和C-端硫酯酶结构域。除了一个以外，所有的合成酶模块都包含完整的剪裁结构域(酮还原酶、脱水酶和烯醇还原酶)，这是通过与已知聚酮合成酶的序列同源性确定的。对该簇的几个关键成分进行了激活位点分析，以进一步验证该基因簇与流感病毒B1的生产有关。这项工作将为更好地理解大内酰胺的形成打开大门，并为基于遗传学的氟病毒素结构多样化提供一条途径。
Fluvirucin B1, produced by Actinomadura vulgaris, is a 14-membered macrolactam active against a variety of infectious fungi as well as influenza A. Despite considerable interest from the synthetic community, very little information is available regarding the biosynthetic origins of the fluvirucins. Herein, we report the identification and initial characterization of the fluvirucin B1 polyketide synthase and related enzymes. The cluster consists of five extender modules flanked by an N-terminal acyl carrier protein and C-terminal thioesterase domain. All but one of the synthase modules contain the full complement of tailoring domains (ketoreductase, dehydratase, and enoyl reductase) as determined by sequence homology with known polyketide synthases. Acitve site analyses of several key components of the cluster are performed to further verify that this gene cluster is associated with production of fluvirucin B1. This work will both open doors toward a better understanding of macrolactam formation and provide an avenue to genetics-based diversification of fluvirucin structure.
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影响因子：
16.8
作者：
Asturias, FJ;Chadick, JZ;Smith, S
通讯作者：
Smith, S
影响因子：
2.1
作者：
Moutevelis-Minakakis, Panagiota;Neokosmidi, Afroditi;Kokotos, George
通讯作者：
Kokotos, George
影响因子：
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作者：
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通讯作者：
OKI, T
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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