TitleIdentification and Biological Activity of NFAT-133 Congeners from .
Publication TypeJournal Article
Year of Publication2021
AuthorsZhou W, Posri P, Liu X-J, Ju Z, Lan W-J, Mahmud T
JournalJ Nat Prod
Volume84
Issue9
Pagination2411-2419
Date Published2021 Sep 24
ISSN1520-6025
KeywordsAnimals, Biological Products, Mice, Molecular Structure, Pentanols, Pentanones, Polyketides, RAW 264.7 Cells, Streptomyces
Abstract

The soil bacterium 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 ATCC 27456 Δ. 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.

DOI10.1021/acs.jnatprod.1c00152
Alternate JournalJ Nat Prod
PubMed ID34519213
PubMed Central IDPMC8577183
Grant ListR01 AI129957 / AI / NIAID NIH HHS / United States
S10 OD018518 / OD / NIH HHS / United States