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Existing approaches use auto\u2010induction media, synthetic cell\u2010cell communication systems, or application\u2010specific biosensors. A simpler, resource\u2010efficient, and general\u2010purpose expression control system responsive to common changes during batch culture would be highly valuable. We used native\n                      <jats:italic>E. coli<\/jats:italic>\n                      promoters, including P\n                      <jats:italic>hdeA<\/jats:italic>\n                      , P\n                      <jats:italic>dpS<\/jats:italic>\n                      , P\n                      <jats:italic>fumA<\/jats:italic>\n                      , P\n                      <jats:italic>rpoA<\/jats:italic>\n                      , P\n                      <jats:italic>rpoS<\/jats:italic>\n                      , P\n                      <jats:italic>gadA<\/jats:italic>\n                      , and P\n                      <jats:italic>yiaG<\/jats:italic>\n                      , and recombinase\u2010based switches to repurpose endogenous transcription signals for control of heterologous gene expression. Specifically, natural changes, covering 1\u20132 orders of magnitude across growth phases, in transcription from endogenous promoters result in recombinase expression at the exponential\u2010to\u2010stationary phase transition. So\u2010expressed recombinases invert a constitutive promoter regulating expression of arbitrary heterologous genes amplifying the endogenous transcriptional input signal by more than 10\u2010fold. We realized reversible and single\u2010use switching with reduced static and dynamic cell\u2010to\u2010cell variation and overall expression amplification. We used \u201coff\u2010the\u2010shelf\u201d genetic parts and abstraction\u2010based composition frameworks to realize reliable forward engineering of our synthetic genetic systems. We engineered autonomous control systems for regulating heterologous gene expression. Our system uses generic endogenous promoters to sense and control heterologous expression during growth\u2010phase transitions. Our system does not require specialized auto\u2010induction media, production or activation of quorum sensing, or the development of application\u2010specific biosensors. Cells programmed to control themselves could simplify existing bioprocess operations and enable the development of more powerful synthetic genetic systems. Modern biotechnology uses engineered microbes to manufacture molecules that are incorporated into medicines, flavors, fuels, and other materials. Making molecules inside cells requires enzymes, whose expression levels and timing need to be optimized to maximize final product yields. Many engineered microbes use enzymes that should only be expressed during the later stages of cell growth to avoid overconsumption of resources or accumulation of toxic intermediates. Here, we develop simple genetic devices that enable engineered cells to control themselves, automatically switching on or off enzyme expression during batch cell culture. Unlike existing approaches, our devices do not require specialized growth media or wasteful synthesis of cell\u2010cell signaling molecule.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bit.70377","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:11:48Z","timestamp":1789020708000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Autonomous Control of Gene Expression Using Endogenous Transcription Signals"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4577-343X","authenticated-orcid":false,"given":"Pakpoom","family":"Subsoontorn","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medical Science Naresuan University Phitsanulok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6952-8098","authenticated-orcid":false,"given":"Drew","family":"Endy","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Stanford University Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-8975","authenticated-orcid":false,"given":"Olivier","family":"Borkowski","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay, INRAE, AgroParisTech, Micalis Institute Jouy\u2010en\u2010Josas France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.64.6.2240-2246.1998"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01739257"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-090110-102946"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1202344109"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232758"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2016.07.009"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.6b00257"},{"key":"e_1_2_9_9_1","first-page":"1527","article-title":"Modulation of Chemical Composition and Other Parameters of the Cell by Growth Rate. 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