对来自反式酰基转移酶模块聚酮合酶的酮合成酶的深入研究。
A close look at a ketosynthase from a trans-acyltransferase modular polyketide synthase.
作者信息
Gay Darren C, Gay Glen, Axelrod Abram J, Jenner Matthew, Kohlhaas Christoph, Kampa Annette, Oldham Neil J, Piel Jörn, Keatinge-Clay Adrian T
机构信息
Department of Molecular Biosciences, The University of Texas at Austin, 1 University Station A5300, Austin, TX 78712, USA.
Department of Chemistry, The University of Texas at Austin, 1 University Station A5300, Austin, TX 78712, USA.
出版信息
Structure. 2014 Mar 4;22(3):444-51. doi: 10.1016/j.str.2013.12.016. Epub 2014 Feb 6.
Abstract
The recently discovered trans-acyltransferase modular polyketide synthases catalyze the biosynthesis of a wide range of bioactive natural products in bacteria. Here we report the structure of the second ketosynthase from the bacillaene trans-acyltransferase polyketide synthase. This 1.95 Å resolution structure provides the highest resolution view available of a modular polyketide synthase ketosynthase and reveals a flanking subdomain that is homologous to an ordered linker in cis-acyltransferase modular polyketide synthases. The structure of the cysteine-to-serine mutant of the ketosynthase acylated by its natural substrate provides high-resolution details of how a native polyketide intermediate is bound and helps explain the basis of ketosynthase substrate specificity. The substrate range of the ketosynthase was further investigated by mass spectrometry.
摘要
最近发现的反式酰基转移酶模块化聚酮合酶催化细菌中多种生物活性天然产物的生物合成。在此，我们报道了来自杆菌烯反式酰基转移酶聚酮合酶的第二种酮合成酶的结构。这种分辨率为1.95 Å的结构提供了模块化聚酮合酶酮合成酶目前最高分辨率的视图，并揭示了一个侧翼亚结构域，该亚结构域与顺式酰基转移酶模块化聚酮合酶中一个有序的连接子同源。被其天然底物酰化的酮合成酶的半胱氨酸到丝氨酸突变体的结构提供了天然聚酮中间体如何结合的高分辨率细节，并有助于解释酮合成酶底物特异性的基础。通过质谱进一步研究了酮合成酶的底物范围。
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