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Although classified as a siderophore, TDA is also produced under iron-replete conditions. To address this paradox, we fused the tdaCDE promoter region of Phaeobacter piscinae S26 with a promoter-less gfp reporter gene to monitor the transcription of TDA biosynthetic genes under different conditions and validated its accuracy using RT-qPCR. In both complex ($\\frac{1}{2}$YTIO) and low-complexity (IOCGH) marine media, iron supplementation repressed tdaCDE transcription and reduced iron-chelation activity. However, TDA production responded differently depending on medium composition: iron suppressed TDA production in IOCGH but increased it in $\\frac{1}{2}$YTIO. Antimicrobial activity of culture supernatants declined in late-stage iron-limited $\\frac{1}{2}$YTIO-based cultures, even though tdaCDE transcription and iron-chelating activity increased. Acidification restored antimicrobial activity and increased detectable TDA levels, while several non-antimicrobial structural analogues\u2014detected by LC-MS in non-acidified samples\u2014diminished upon acidification, suggesting pH-driven interconversion. These findings reveal that TDA biosynthesis is regulated by iron availability but that the antimicrobial output of the producer depends on medium composition and pH-driven chemical transformations between TDA and its related structural analogues.<\/jats:p>","DOI":"10.1093\/femsec\/fiag080","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:43:38Z","timestamp":1784288618000},"source":"Crossref","is-referenced-by-count":1,"title":["Re-examining the iron paradox: the influence of growth medium on regulation and functionality of the tropodithietic acid (TDA) biosynthetic pathway in\n                    <i>Phaeobacter piscinae<\/i>"],"prefix":"10.1093","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8947-1056","authenticated-orcid":false,"given":"Lauge","family":"Alfastsen","sequence":"first","affiliation":[{"name":"Center for Microbial Secondary Metabolites (CeMiSt), Department of Biotechnology and Biomedicine, Technical University 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