Bacterial cell envelope polymers are often modified with acyl esters that modulate physiology, enhance pathogenesis and provide antibiotic resistance. Here, using the d-alanylation of lipoteichoic acid (Dlt) pathway as a paradigm, we have identified a widespread strategy for how acylation of cell envelope polymers occurs. In this strategy, a membrane-bound O-acyltransferase (MBOAT) protein transfers an acyl group from an intracellular thioester onto the tyrosine of an extracytoplasmic C-terminal hexapeptide motif. This motif shuttles the acyl group to a serine on a separate transferase that moves the cargo to its destination. In the Dlt pathway, here studied in Staphylococcus aureus and Streptococcus thermophilus, the C-terminal ‘acyl shuttle’ motif that forms the crucial pathway intermediate is found on a transmembrane microprotein that holds the MBOAT protein and the other transferase together in a complex. In other systems, found in both Gram-negative and Gram-positive bacteria as well as some archaea, the motif is fused to the MBOAT protein, which interacts directly with the other transferase. The conserved chemistry uncovered here is widely used for acylation throughout the prokaryotic world.

细菌细胞包膜聚合物通常用酰基酯进行修饰，以调节生理机能、增强发病机制并提供抗生素耐药性。在这里，使用脂磷壁酸（Dlt）途径的d-丙氨酰化作为范例，我们已经确定了细胞包膜聚合物酰化如何发生的广泛策略。在该策略中，膜结合O -酰基转移酶 (MBOAT) 蛋白将酰基从细胞内硫酯转移到胞质外 C 端六肽基序的酪氨酸上。该基序将酰基运送到单独的转移酶上的丝氨酸，将货物移动到目的地。在金黄色葡萄球菌和嗜热链球菌的Dlt 途径中，在跨膜微生物蛋白上发现了形成关键途径中间体的 C 端“酰基穿梭”基序，该跨膜微生物蛋白将 MBOAT 蛋白和其他转移酶结合在一起形成复合物。在革兰氏阴性和革兰氏阳性细菌以及一些古细菌中发现的其他系统中，该基序与 MBOAT 蛋白融合，该蛋白直接与其他转移酶相互作用。这里发现的保守化学广泛用于整个原核世界的酰化。