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Herein, we report their distinct substrate allosteric recognition and enantioselective reduction mechanisms. FabG achieves allosteric regulation of ACP and NADPH through ACP binding across two adjacent FabG monomers, while FabI follows an irreversible compulsory order of substrate binding in that NADH binding must precede that of ACP on a discrete FabI monomer. Moreover, FabG and FabI utilize a backdoor residue Phe187 or a \u201crheostat\u201d \u03b18 helix for acyl chain length selection, and their corresponding triad residues Ser142 or Tyr145 recognize the keto\u2010 or enoyl\u2010acyl substrates, respectively, facilitating initiation of nucleophilic attack by NAD(P)H. The other two triad residues (Tyr and Lys) mediate subsequent proton transfer and (\n                    <jats:italic>R<\/jats:italic>\n                    )\u20103\u2010hydroxyacyl\u2010 or saturated acyl\u2010ACP production.\n                  <\/jats:p>","DOI":"10.1002\/anie.202313109","type":"journal-article","created":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T22:34:40Z","timestamp":1696199680000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The Molecular Basis of Catalysis by SDR Family Members Ketoacyl\u2010ACP Reductase FabG and Enoyl\u2010ACP Reductase FabI in Type\u2010II Fatty Acid Biosynthesis"],"prefix":"10.1002","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1277-0654","authenticated-orcid":false,"given":"Jiashen","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Chemical Biology State Key Laboratory of Systems Medicine for Cancer 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