Biosynthesis of the Nuclear Factor of Activated T Cells Inhibitor NFAT-133 in Streptomyces pactum.

ABSTRACT: NFAT-133 is a Streptomyces-derived aromatic polyketide compound with immunosuppressive, antidiabetic, and antitrypanosomal activities. It inhibits transcription mediated by nuclear factor of activated T cells (NFAT), leading to the suppression of interleukin-2 expression and T cell proliferation. It also activates the AMPK pathway in L6 myotubes and increases glucose uptake. In addition to NFAT-133, a number of its congeners, e.g., panowamycins and benwamycins, have been identified. However, little is known about their modes of formation in the producing organisms. Through genome sequencing of Streptomyces pactum ATCC 27456, gene inactivation, and genetic complementation experiments, the biosynthetic gene cluster of NFAT-133 and its congeners has been identified. The cluster

SUBMITTER: Zhou W 

PROVIDER: S-EPMC7891853 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature