SAXS reveals highly flexible interdomain linkers of tandem acyl carrier protein-thioesterase domains from a fungal nonreducing polyketide synthase
SAXS reveals highly flexible interdomain linkers of tandem acyl carrier protein-thioesterase domains from a fungal nonreducing polyketide synthase
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DOI：
10.1002/1873-3468.13954
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发表时间：
2020-10-26
期刊：
影响因子：
3.5
通讯作者：
Wattana-Amorn, Pakorn
中科院分区：
文献类型：
--
作者：
Bunnak, Waraporn;Winter, Ashley J.;Wattana-Amorn, Pakorn
半月板视蛋白A（Menisporopsin A）是一种具有生物活性的真菌大环聚内酯，其生物合成仅需要还原性（R）和非还原性（NR）聚酮酶（PKS）来指导一系列酯化和环内酯化反应。没有关于这些PKS的结构信息。在这里，我们报告的单和双态酰基载体蛋白（ACP（2）和ACP（1）-ACP（2））-硫酯酶（TE）结构域从NR-PKS参与视孔蛋白A的生物合成的溶液特性。小角X射线散射（SAXS）研究结合同源性建模揭示，这些多肽采用独特的珠串配置，其特征在于存在高度灵活的域间连接。这些模型为研究真菌NR-PKS的结构域组织和结构域间相互作用提供了一个平台，这可能对指导功能优化的聚酮支架的设计具有价值。
Menisporopsin A is a fungal bioactive macrocyclic polylactone, the biosynthesis of which requires only reducing (R) and nonreducing (NR) polyketide synthases (PKSs) to guide a series of esterification and cyclolactonization reactions. There is no structural information pertaining to these PKSs. Here, we report the solution characterization of singlet and doublet acyl carrier protein (ACP(2) and ACP(1)-ACP(2))-thioesterase (TE) domains from NR-PKS involved in menisporopsin A biosynthesis. Small-angle X-ray scattering (SAXS) studies in combination with homology modelling reveal that these polypeptides adopt a distinctive beads-on-a-string configuration, characterized by the presence of highly flexible interdomain linkers. These models provide a platform for studying domain organization and interdomain interactions in fungal NR-PKSs, which may be of value in directing the design of functionally optimized polyketide scaffolds.