Understanding biosynthetic protein-protein interactions.
Understanding biosynthetic protein-protein interactions.
复制标题
了解生物合成蛋白质-蛋白质相互作用。
DOI：
10.1039/c8np90037j
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发表时间：
2018
影响因子：
11.9
通讯作者：
Ackerley DF
中科院分区：
文献类型：
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作者：
Ackerley DF
查看日志|查看问题域，进行多轮扩链和Modi阳离子。迭代PKS可分为I型(载体蛋白和催化结构域被结合到单个多酶中)或II型(独立载体蛋白和几个不同的催化亚基)。在同样催化迭代链组装的类似的FAS系统中，观察到相同的分为I型和II型结构。Herbst，Townsend和Maier(DOI：10.1039/c8np00039e)讨论了I型PKSS和FASS功能的核心PPI，而Burkart等人讨论了PPI。重点是第二类系统(DOI：10.1039/c8np00040a)。PKS装配线的显著复杂性被其代谢产品的结构复杂性所反映，这使得这些分子在商业相关规模上的化学合成具有挑战性。因此，设计这样的装配线以生产高滴度的新型聚酮衍生物是LD的高度优先事项。Klaus和Grininger(DOI：10.1039/c8np00030a)对当前的方法进行了评估。除了各种不同类型的Fas和PKS装配线外，NRPS还采用了基于载体蛋白的酶逻辑。与PKSS和FASs不同的是，PKSS和FASs对生物合成中间体具有多个共价结合位点(如载体蛋白、AT活性位点和酮合成酶活性位点)，而NRPS载体蛋白是中间体在整个肽链组装过程中唯一的共价结合位点。这些系统的寡聚状态也不同，I型PKS和Fas亚基通常形成同源二聚体，而NRPS亚基被认为是作为单体发挥作用。因此，连接这些系统似乎是困难的，但事实上，许多PKS-NRPS混合系统是已知的。江口等人讨论了对混合装配线和支撑其功能的PPI的理解状况(DOI：10.1039/c8np00022k)。在对纯PPI系统的关注中，Izoré和(DOI：10.1039/c8np00038g)讨论了载体蛋白在调节PPI中所起的中心作用，而Ackerley等人(DOI：10.1039/c8np00036k)讨论了NRPS工程的方法，他们强调了维护关键的PPI接口对于创建生产性工程装配线的重要性。将范围扩展到超同步(ET)ASE范式之外，Laursen
View Journal| View Issue domains to carry out multiple rounds of chain extension and modi cation. Iterative PKSs can be classed as either type I (where the carrier protein and catalytic domains are incorporated into a single multienzyme) or type II (a standalone carrier protein and several distinct catalytic subunits). In the analogous FAS systems, which also catalyse iterative chain assembly, the same division into type I and type II architectures is observed. The PPIs central to the function of type I PKSs and FASs are discussed by Herbst, Townsend and Maier (DOI: 10.1039/c8np00039e), while Burkart et al. focus on the type II systems (DOI: 10.1039/c8np00040a). The remarkable complexity of PKS assembly lines is re ected by the structural complexity of their metabolic products, which o en makes chemical synthesis of these molecules on commercially-relevant scales challenging. Engineering of such assembly lines to produce novel polyketide derivatives in high titres is thus a high priority for the eld. Current approaches for this are evaluated by Klaus and Grininger (DOI: 10.1039/c8np00030a). In addition to the various different types of FAS and PKS assembly lines, NRPSs also employ carrier protein-based enzymatic logic. In contrast to PKSs andFASs, which possess several covalent attachment sites (such as the carrier protein, AT active site and ketosynthase active site) for biosynthetic intermediates, NRPS carrier proteins act as the sole site for covalent attachment of intermediates throughout the peptide chain assembly. The oligomerisation states of these systems also differ, with type I PKS and FAS subunits typically forming homodimers, whereas NRPS subunits are believed to function as monomers. Concatenating these systems would therefore appear to be difficult, but in fact numerous hybrid PKS–NRPS systems are known. The state of understanding of hybrid assembly lines and the PPIs underpinning their function is discussed by Eguchi et al.(DOI: 10.1039/c8np00022k). Shi ing the focus to pure NRPS systems, the central role played by the carrier protein in mediating PPIs is discussed by Izoré and Cryle (DOI: 10.1039/c8np00038g), while approaches to NRPS engineering are discussed by Ackerley et al.(DOI: 10.1039/c8np00036k), who emphasise the importance of maintaining key PPI interfaces for the creation of productive engineered assembly lines. Expanding the scope beyond the megasynth (et) ase paradigm, Laursen