biostudies-literatureZhou WNational Institute of Allergy and Infectious DiseasesThailand Science Research and InnovationNIAID NIH HHSNational Natural Science Foundation of ChinaNIH HHS2411-2419https://www.ebi.ac.uk/biostudies/studies/S-EPMC8577183biostudies-literatureUnknown84(9)The soil bacterium <i>Streptomyces pactum</i> ATCC 27456 produces a number of polyketide natural products. Among them is NFAT-133, an inhibitor of the nuclear factor of activated T cells (NFAT) that suppresses interleukin-2 (IL-2) expression and T cell proliferation. Biosynthetic gene inactivation in the ATCC 27456 strain revealed the ability of this strain to produce other polyketide compounds including analogues of NFAT-133. Consequently, seven new derivatives of NFAT-133, TM-129-TM-135, together with a known compound, panowamycin A, were isolated from the culture broth of <i>S. pactum</i> ATCC 27456 Δ<i>ptmTDQ</i>. Their chemical structures were elucidated on the basis of their HRESIMS, 1D and 2D NMR spectroscopy, and ECD calculation and spectral data. NFAT-133, TM-132, TM-135, and panowamycin A showed no antibacterial activity or cytotoxicity, but weakly reduced the production of LPS-induced nitric oxide in RAW264.7 cells in a dose-dependent manner. A revised chemical structure of panowamycin A and proposed modes of formation of the new NFAT-133 analogues are also presented.Journal of natural productsIdentification and Biological Activity of NFAT-133 Congeners from <i>Streptomyces pactum</i>.PMC8577183S10 OD018518AI12995781872795R01 AI129957PHD/0007/2558Lan WJJu ZLiu XJMahmud TZhou WPosri PfalseIdentification and Biological Activity of NFAT-133 Congeners from <i>Streptomyces pactum</i>.The soil bacterium <i>Streptomyces pactum</i> ATCC 27456 produces a number of polyketide natural products. Among them is NFAT-133, an inhibitor of the nuclear factor of activated T cells (NFAT) that suppresses interleukin-2 (IL-2) expression and T cell proliferation. Biosynthetic gene inactivation in the ATCC 27456 strain revealed the ability of this strain to produce other polyketide compounds including analogues of NFAT-133. Consequently, seven new derivatives of NFAT-133, TM-129-TM-135, together with a known compound, panowamycin A, were isolated from the culture broth of <i>S. pactum</i> ATCC 27456 Δ<i>ptmTDQ</i>. Their chemical structures were elucidated on the basis of their HRESIMS, 1D and 2D NMR spectroscopy, and ECD calculation and spectral data. NFAT-133, TM-132, TM-135, and panowamycin A showed no antibacterial activity or cytotoxicity, but weakly reduced the production of LPS-induced nitric oxide in RAW264.7 cells in a dose-dependent manner. A revised chemical structure of panowamycin A and proposed modes of formation of the new NFAT-133 analogues are also presented.2021-01-01T00:00:00Z2021 Sep2025-04-04T13:57:39.762Z2025-04-04T13:57:39.762ZS-EPMC85771833451921310.1021/acs.jnatprod.1c00152