�鶹��Ժ

Researchers reveal acyl chain length-dependent conformational dynamics of acyl carrier protein

Acyl carrier protein (ACP) plays a central role in fatty acid biosynthesis, acting as a molecular "shuttle" that carries, protects, and delivers elongating acyl chains to various enzymatic partners. However, the high flexibility of ACP and the instability of its thioester‐linked intermediates have long hindered detailed structural characterization of its dynamic behavior.

In a study published in the , a team led by Prof. Wang Fangjun from the Dalian Institute of Chemical �鶹��Ժics of the Chinese Academy of Sciences revealed how ACP adapts its conformation to accommodate acyl chains of varying lengths (C4-C18), and revealed acyl chain length-dependent conformational dynamics of ACP at the molecular level.

Researchers used native mass spectrometry (nMS) to selectively isolate and enrich chemically unstable acyl‐ACP intermediates in an ion trap, followed by 193 nm ultraviolet photodissociation (UVPD) to probe their conformational dynamics.

They discovered a striking acyl chain length-dependent rearrangement: Shorter acyl chains (C4-C10) reside in a primary hydrophobic subpocket (Subpocket I), while longer chains (C10-C18) bend and extend into a second subpocket (Subpocket II).

Structural analysis identified Phe50 and Ile62 as critical "gates" that modulate the hydrophobic cavity's dimensions. In addition, Loop I and the Thr64-Gln66 segment were shown to play essential roles in stabilizing longer chains (C12-C18) intermediates.

"Our study provides molecular‐level insight into how ACP adapts to acyl chains of different lengths," said Prof. Wang. "The findings set the stage for the rational redesign of ACP to enhance the biosynthesis of target fatty acids, particularly medium‐chain species (C8-C12) with high industrial value."