Identification and Biological Activity of NFAT-133 Congeners from Streptomyces pactum.

Identification and Biological Activity of NFAT-133 Congeners from Streptomyces pactum.
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棕榈链霉菌NFAT-133同源物的鉴定及生物活性研究

DOI:
10.1021/acs.jnatprod.1c00152
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发表时间:
2021-09-24
影响因子:
5.1
通讯作者:
Mahmud T
Mahmud T
中科院分区:
生物学2区
文献类型:
--
作者:
Zhou W;Posri P;Liu XJ;Ju Z;Lan WJ;Mahmud T

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土壤细菌棕榈链霉菌ATCC 27456产生许多聚酮类天然产物。其中包括NFAT-133,它是活化T细胞核因子(NFAT)的抑制剂,可抑制白细胞介素-2 (IL-2)的表达和T细胞增殖。ATCC 27456菌株的生物合成基因失活表明,该菌株能够产生包括NFAT-133类似物在内的其他聚酮化合物。因此,从葡萄球菌ATCC 27456 ΔptmTDQ的培养液中分离出7个新的NFAT-133、TM-129 - TM-135衍生物和已知化合物panowamycin a。根据hremus、1D和2D NMR、ECD计算和光谱数据对它们的化学结构进行了分析。NFAT-133、TM-132、TM-135和panowamycin A对RAW264.7细胞无抑菌活性和细胞毒性,但能弱减弱lps诱导的一氧化氮(no)的产生,且呈剂量依赖性。修订的panowamycin A的化学结构,并提出了新的NFAT-133类似物的形成模式。
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 (NO) 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.
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