Decrypting the oscillating nature of the 4′‐phosphopantetheine arm in acyl carrier protein AcpM of <i>Mycobacterium tuberculosis</i>

In Mycobacterium tuberculosis , acyl carrier protein (AcpM)‐mediated fatty acid synthase type II is integral for the synthesis of mycolic acids. AcpM, designated as an atypical ACP, comprises of a putative 33 amino acid long C‐terminal extension which is distinctive in nature. Here, we aimed at devising an ‘easy‐to‐go’ method for the generation of crypto‐AcpM loaded with a solvatochromic probe 7‐Nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl, which is linked to the 4′‐phosphopantetheine (Ppant) prosthetic group of AcpM. The crypto‐AcpM, coupled with fluorescence spectroscopy and molecular dynamics simulation studies, was employed to explore the elusive dynamics of Ppant arm in AcpM. This investigation establishes the role of the flexible C‐terminal extension of AcpM in regulating the prosthetic group sequestration ability by modulating the ‘Asp‐Ser‐Leu’ motif.