The soil bacterium Streptomyces pactum 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 S. pactum ATCC 27456 ΔptmTDQ. 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.

中文翻译：

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来自 Streptomyces pactum 的 NFAT-133 同源物的鉴定和生物活性

土壤细菌Streptomyces pactum ATCC 27456 产生许多聚酮化合物天然产物。其中包括 NFAT-133，一种活化 T 细胞核因子 (NFAT) 的抑制剂，可抑制白细胞介素 2 (IL-2) 表达和 T 细胞增殖。ATCC 27456 菌株中的生物合成基因失活揭示了该菌株产生其他聚酮化合物的能力，包括 NFAT-133 的类似物。因此，从S. pactum ATCC 27456 Δ ptmTDQ的培养液中分离出 NFAT-133 的七种新衍生物 TM-129–TM-135 以及已知化合物 panowamycin A. 基于它们的 HRESIMS、1D 和 2D NMR 光谱以及 ECD 计算和光谱数据阐明了它们的化学结构。NFAT-133、TM-132、TM-135 和 panowamycin A 没有显示出抗菌活性或细胞毒性，但以剂量依赖性方式微弱地降低了 LPS 诱导的 RAW264.7 细胞中一氧化氮的产生。还介绍了帕诺瓦霉素 A 的修订化学结构和新 NFAT-133 类似物的建议形成模式。