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| Title | Structure and catalytic mechanism of exogenous fatty acid recycling by AasS, a versatile acyl-ACP synthetase. |
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| Journal, issue, pages | Nat Struct Mol Biol, Vol. 32, Issue 5, Page 802-817, Year 2025 |
| Publish date | Jan 10, 2025 |
 Authors | Haomin Huang / Chen Wang / Shenghai Chang / Tao Cui / Yongchang Xu / Man Huang / Huimin Zhang / Chun Zhou / Xing Zhang / Youjun Feng /   |
| PubMed Abstract | Fatty acids (FAs) are essential building blocks for all the domains of life, of which bacterial de novo synthesis, called type II FA synthesis (FAS II), is energetically expensive. The recycling of ...Fatty acids (FAs) are essential building blocks for all the domains of life, of which bacterial de novo synthesis, called type II FA synthesis (FAS II), is energetically expensive. The recycling of exogenous FAs (eFAs) partially relieves the FAS II demand and, therefore, compromises the efficacy of FAS II-directed antimicrobials. The versatile acyl-acyl carrier protein (ACP) synthetase, AasS, enables bacterial channeling of diverse eFA nutrients through holo-ACP, an activated form of ACP. However, the molecular mechanism for AasS catalysis is not fully understood. Here we report a series of cryo-electron microscopy structures of AasS from the bioluminescent bacterium Vibrio harveyi to provide insights into the catalytic cycle. AasS forms a ring-shaped hexamer, with each protomer folding into two distinct domains. Biochemical and structural analysis suggests that AasS accommodates distinct eFA substrates and the conserved W230 residue has a gating role. Adenosine triphosphate and Mg binding converts the AasS hexamer to a tetramer, which is likely needed for the acyl adenylate intermediate formation. Afterward, AasS reverts to the hexamer conformation in adaption to acyl-ACP production. The complete landscape for eFA scavenging lays a foundation for exploiting the versatility of AasS in biopharmaceuticals. |
 External links | Nat Struct Mol Biol / PubMed:39794554 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.41 - 2.76 Å |
| Structure data | EMDB-35144, PDB-8i35: EMDB-35153, PDB-8i3i: EMDB-35165: Acyl-ACP synthetase structure bound to ATP. EMDB-35190, PDB-8i51: EMDB-35200, PDB-8i6m: EMDB-35248, PDB-8i8d: EMDB-35249, PDB-8i8e: |
| Chemicals |  ChemComp-OLA:  ChemComp-MG:  ChemComp-ANP:  ChemComp-ATP:  ChemComp-AMP:  ChemComp-OP3:  ChemComp-PN7: |
| Source |
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 Keywords | CYTOSOLIC PROTEIN / Acyl-ACP synthetase / Tool enzyme / TRANSFERASE / CYTOSOLIC PROTEIN/TRANSPORT PROTEIN / Ligase / CYTOSOLIC PROTEIN-TRANSPORT PROTEIN complex / TRANSPORT PROTEIN/CYTOSOLIC PROTEIN / TRANSPORT PROTEIN-CYTOSOLIC PROTEIN complex |
vibrio harveyi (bacteria)
escherichia coli (E. coli)