Wang Xinzhu, Zhao Liya, Liu Chao, Qi Jun, Zhao Peipei, Liu Zhaoming, Li Chunlei, Hu Yingying, Yin Xin, Liu Xin, Liao Zhixin, Zhang Lixin, Xia Xuekui
Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Southeast University, Nanjing, China.
Shandong Provincial Key Laboratory for Biosensor, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.
Front Microbiol. 2020 Jan 15;10:2958. doi: 10.3389/fmicb.2019.02958. eCollection 2019.
Cycloaddition reactions such as intramolecular Diels-Alder (IMDA) are extremely important in constructing multicyclic scaffolds with diverse bioactivities. Using MycB as a biomarker, three new polyketides - Chaetolivacines A (), B (), and C () - with one known compound Myceliothermophin E () comprising of decalin and 4-hydroxy-2-pyridones were obtained from the culture of SD-80A under the guidance of gene mining. The structures of these compounds were established using detailed 1D, 2D NMR, and high-resolution electron spray ionization mass spectroscopy (HRESIMS) analysis. The relative and absolute configurations of the compounds , , and were elucidated by NOESY and ECD. The biosynthesis pathways of these compounds were proposed, which involves in three key genes [polyketide synthase-non-ribosomal peptide synthetases (PKS-NRPS)], , and . Compounds - were tested for their antimicrobial activities, and compounds and showed moderate bioactivity against (SA) and methicillin-resistant (MRSA) with MIC values of 15.8 and 27.1 μM. The results showed that configuration of C-21 in and is important for anti-SA and anti-MRSA activities. This study reveals the significant potential of the genus in producing new PKS-NRPS, therefore increasing the speed in the mining for new sources of antimicrobial agents.
分子内狄尔斯-阿尔德（IMDA）等环加成反应在构建具有多种生物活性的多环支架方面极为重要。以MycB作为生物标志物，在基因挖掘的指导下，从SD - 80A的培养物中获得了三种新的聚酮化合物——Chaetolivacines A（）、B（）和C（），以及一种已知化合物Myceliothermophin E（），它们由十氢化萘和4 - 羟基 - 2 - 吡啶酮组成。这些化合物的结构通过详细的一维、二维核磁共振以及高分辨率电子喷雾电离质谱（HRESIMS）分析得以确定。化合物、和的相对和绝对构型通过NOESY和ECD得以阐明。提出了这些化合物的生物合成途径，该途径涉及三个关键基因[聚酮合酶 - 非核糖体肽合成酶（PKS - NRPS）]、和。对化合物 - 的抗菌活性进行了测试，化合物和对金黄色葡萄球菌（SA）和耐甲氧西林金黄色葡萄球菌（MRSA）表现出中等生物活性，MIC值分别为15.8和27.1 μM。结果表明，和中C - 21的构型对于抗SA和抗MRSA活性很重要。这项研究揭示了属在产生新的PKS - NRPS方面的巨大潜力，从而加快了抗菌剂新来源的挖掘速度。
