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In\n                    <jats:italic>P. horikoshii<\/jats:italic>\n                    genome, the BAR gene (\n                    <jats:italic>PH0138<\/jats:italic>\n                    ) forms a cluster with\n                    <jats:italic>PH0137<\/jats:italic>\n                    , which encodes a putative transporter protein, and\n                    <jats:italic>PH0140<\/jats:italic>\n                    that encodes a feast\/famine regulatory protein (FFRP), involved in the transcriptional regulation of metabolic pathway genes. Here, we performed gene expression, protein\u2013DNA interaction, and crystallographic analyses to elucidate the expression mechanism of the BAR cluster. Gene expression analysis revealed that\n                    <jats:sc>d<\/jats:sc>\n                    \u2010\n                    <jats:italic>allo<\/jats:italic>\n                    \u2010Ile simultaneously induces\n                    <jats:italic>PH0138<\/jats:italic>\n                    and\n                    <jats:italic>PH0137<\/jats:italic>\n                    . Electrophoretic mobility shift assays demonstrated that the PH0140 protein binds to the\n                    <jats:italic>PH0137<\/jats:italic>\n                    promoter in the presence of\n                    <jats:sc>l<\/jats:sc>\n                    \u2010Ile, but this interaction is disrupted by\n                    <jats:sc>d<\/jats:sc>\n                    \u2010\n                    <jats:italic>allo<\/jats:italic>\n                    \u2010Ile, identifying PH0140 as a\n                    <jats:sc>d<\/jats:sc>\n                    \u2010amino acid\u2010responsive regulatory protein (DARP). The crystal structures of DARP bound to\n                    <jats:sc>l<\/jats:sc>\n                    \u2010Ile and\n                    <jats:sc>d<\/jats:sc>\n                    \u2010\n                    <jats:italic>allo<\/jats:italic>\n                    \u2010Ile were compared with those of another FFRP family member,\n                    <jats:italic>P. horikoshii<\/jats:italic>\n                    FL11. Our findings reveal a dimeric arrangement of\n                    <jats:sc>l<\/jats:sc>\n                    \u2010Ile\u2010bound DARP resembling the DNA\u2010bound (open) form of FL11, whereas\n                    <jats:sc>d<\/jats:sc>\n                    \u2010\n                    <jats:italic>allo<\/jats:italic>\n                    \u2010Ile\u2010bound DARP corresponds to the DNA\u2010unbound (closed) form. These conformational changes result from subtle alterations in hydrogen bonding around the coregulators. Furthermore, cultivation in\n                    <jats:sc>d<\/jats:sc>\n                    \u2010\n                    <jats:italic>allo<\/jats:italic>\n                    \u2010Ile substitution medium only impacted the expression of\n                    <jats:italic>PH0138<\/jats:italic>\n                    and\n                    <jats:italic>PH0137<\/jats:italic>\n                    , and not the other genes, suggesting that DARP regulates a more limited gene set than FL11. Cumulatively, these results reveal a distinct mechanism by which an FFRP homolog controls\n                    <jats:sc>d<\/jats:sc>\n                    \u2010amino acid utilization.\n                  <\/jats:p>","DOI":"10.1111\/febs.70545","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:40:59Z","timestamp":1776386459000},"page":"5881-5897","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A distinct gene expression mechanism for\n                    <scp>d<\/scp>\n                    \u2010amino acid utilization in hyperthermophilic archaeon\n                    <i>Pyrococcus horikoshii<\/i>"],"prefix":"10.1111","volume":"293","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0659-7226","authenticated-orcid":false,"given":"Ryushi","family":"Kawakami","sequence":"first","affiliation":[{"name":"Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences Tokushima University  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Kawase","sequence":"additional","affiliation":[{"name":"Division of Bioresource Science, Graduate School of Sciences and Technology for Innovation Tokushima University  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taira","family":"Uehara","sequence":"additional","affiliation":[{"name":"Division of Bioresource Science, Graduate School of Sciences and Technology for Innovation Tokushima University  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9951-173X","authenticated-orcid":false,"given":"Haruhiko","family":"Sakuraba","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Science, Faculty of Agriculture Kagawa University  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9315-5383","authenticated-orcid":false,"given":"Tomohiko","family":"Matsuzawa","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Science, Faculty of Agriculture Kagawa University  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6447-1600","authenticated-orcid":false,"given":"Junji","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences Tokushima University  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihisa","family":"Ohshima","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Engineering Osaka Institute of Technology  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