biostudies-literatureUnknownCordoza JLNIGMS NIH HHSActinobacteria are a rich source of bioactive compounds and unique biosynthetic chemistry. <i>Micromonospora echinospora</i> subsp. <i>challisensis</i> NRRL 12255 produces the aromatic polyketide TLN-05220, which exhibits nanomolar activity against antibiotic-resistant human pathogens including vancomycin-resistant <i>Enterococcus faecalis</i> and methicillin-resistant <i>Staphylococcus aureus</i>. The pentangular polyphenol core of TLN-05220 is decorated with a piperazinone moiety, yet the enzymes responsible for the construction of this uncommon modification from amino acid precursors are unknown. Synthetic piperazinone-containing molecules have diverse antimicrobial, antiviral, anticancer, and anti-inflammatory bioactivity profiles, and determining biosynthetic routes for the assembly obioRxiv : the preprint server for biology2025.10.30.685158https://www.ebi.ac.uk/biostudies/studies/S-EPMC12636320biostudies-literatureIntegrated metabolomic and genomic insights into amino acid incorporation within the hybrid polyketide-alkaloid antibiotic TLN-05220.PMC12636320R01 GM125943Sanchez LMNicholas JCHorta CAOwen DMCalhoun JTRodriguez-Velandia LCordoza JLMcKinnie SMKJohnson RAWatts KRLuu GTPetukhova VZWhiteley AEfalseIntegrated metabolomic and genomic insights into amino acid incorporation within the hybrid polyketide-alkaloid antibiotic TLN-05220.Actinobacteria are a rich source of bioactive compounds and unique biosynthetic chemistry. <i>Micromonospora echinospora</i> subsp. <i>challisensis</i> NRRL 12255 produces the aromatic polyketide TLN-05220, which exhibits nanomolar activity against antibiotic-resistant human pathogens including vancomycin-resistant <i>Enterococcus faecalis</i> and methicillin-resistant <i>Staphylococcus aureus</i>. The pentangular polyphenol core of TLN-05220 is decorated with a piperazinone moiety, yet the enzymes responsible for the construction of this uncommon modification from amino acid precursors are unknown. Synthetic piperazinone-containing molecules have diverse antimicrobial, antiviral, anticancer, and anti-inflammatory bioactivity profiles, and determining biosynthetic routes for the assembly o2025-01-01T00:00:00Z2025 Oct2026-06-19T03:17:02.012Z2026-06-19T03:07:09.118ZS-EPMC126363204127985410.1101/2025.10.30.685158