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They produce saturated fatty acids with defined chain length and release them as coenzyme A\u2010conjugates. How they recognize appropriate acyl length to initiate the process of product release is unknown. Here, we resolved two intermediate state structures of FAS, one from each of the two organisms: bacterium\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    and yeast\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    . These structures reveal how acyl carrier protein (ACP) domain and nascent fatty acids interact with the substrate\u2010promiscuous malonyl\u2013palmitoyl transferase (MPT) domain that is involved in product cleavage from the enzyme. MPT adopts a transient channel necessary for the accommodation of long\u2010chain fatty acids. This channel is formed by the transient retraction of a conserved arginine side chain involved in malonate binding. These insights uncover structural determinants that enable\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    type I FAS to produce very long\u2010chain fatty acids used for evading host immunity in tuberculosis (TB).\n                  <\/jats:p>","DOI":"10.1002\/pro.70412","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T13:32:11Z","timestamp":1766410331000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Structural basis of product recognition by\n                    <i>Mycobacterium tuberculosis<\/i>\n                    fatty acid synthase"],"prefix":"10.1002","volume":"35","author":[{"given":"Elnaz Khalili","family":"Samani","sequence":"first","affiliation":[{"name":"Department of Medical Biophysics University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S M Naimul","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander F. 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