Schultz Bailey J, Walker Suzanne
Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts 02115, United States.
Biochemistry. 2025 Apr 15;64(8):1728-1749. doi: 10.1021/acs.biochem.4c00731. Epub 2025 Apr 2.
Cell surface oligosaccharides and related polymers are commonly decorated with acyl esters that alter their structural properties and influence their interactions with other molecules. In many cases, these esters are added to polymers that are already positioned on the extracytoplasmic side of a membrane, presenting cells with a chemical challenge because the high-energy acyl donors used for these modifications are made in the cytoplasm. How activated acyl groups are passed from the cytoplasm to extra-cytoplasmic polymers has been a longstanding question. Recent mechanistic work has shown that many bacterial acyl transfer pathways operate by shuttling acyl groups through two covalent intermediates to their final destination on an extracellular polymer. Key to these and other pathways are cross-membrane acyltransferases─enzymes that catalyze transfer of acyl groups from a donor on one side of the membrane to a recipient on the other side. Here we review what has been learned recently about how cross-membrane acyltransferases in polymer acylation pathways function, highlighting the chemical and biosynthetic logic used by two key protein families, membrane-bound -acyltransferases (MBOATs) and acyltransferase-3 (AT3) proteins. We also point out outstanding questions and avenues for further exploration.
细胞表面寡糖和相关聚合物通常带有酰基酯修饰，这些修饰会改变其结构特性并影响它们与其他分子的相互作用。在许多情况下，这些酯会添加到已经位于细胞膜外质侧的聚合物上，这给细胞带来了化学难题，因为用于这些修饰的高能酰基供体是在细胞质中合成的。活化的酰基如何从细胞质传递到细胞外聚合物一直是个长期存在的问题。最近的机制研究表明，许多细菌的酰基转移途径是通过将酰基穿梭于两个共价中间体，最终到达细胞外聚合物上的最终目的地来运作的。这些途径以及其他途径的关键是跨膜酰基转移酶——催化酰基从膜一侧的供体转移到另一侧受体的酶。在这里，我们回顾了最近在聚合物酰化途径中的跨膜酰基转移酶如何发挥作用方面所学到的知识，重点介绍了两个关键蛋白家族，即膜结合的β-酰基转移酶（MBOATs）和酰基转移酶-3（AT3）蛋白所使用的化学和生物合成逻辑。我们还指出了悬而未决的问题和进一步探索的途径。
