Abstract：
A library of fungi previously recovered from the gastrointestinal tract (GIT) of several fresh, commercially sourced Australian mullet fish was re-profiled for production of a rare class of phenylpropanoid piperazine alkaloids (chrysosporazines) using an integrated platform of; (i) miniaturized 24-well plate cultivation profiling (MATRIX), (ii) UPLC-DAD and UPLC-QTOF-MS/MS (GNPS) chemical profiling, and; (iii) precursor directed biosynthesis to manipulate in situ biosynthetic performance and outputs; to detect two new fungal producers of chrysosporazines. Chemical analysis of an optimized PDA solid phase cultivation of Aspergillus sp. CMB-F661 yielded the new regioisomeric chrysosporazine T (1) and U (2), while precursor directed cultivation amplified production and yielded the very minor new natural products azachrysosporazine T1 (3) and U1 (4), and the new unnatural analogues neochrysosporazine R (5) and S (6). Likewise, chemical analysis of an optimized M1 solid phase cultivation of Spiromastix sp. CMB-F455 lead to the GNPS detection of multiple chrysosporazines and brasiliamides, and the isolation and structure elucidation of chrysosporazine D (7) and brasiliamide A (8). Access to new chrysosporazine regioisomers facilitated structure activity relationship investigations to better define the chrysosporazine P-glycoprotein (P-gp) inhibitory pharmacophore, which is exceptionally potent at reversing doxorubrin resistance in P-gp over expressing colon carcinoma cells (SW600 Ad300).
摘要：
先前从胃肠道（GIT）中回收的几种新鲜真菌库，使用以下集成平台对商业来源的澳大利亚乌鱼鱼进行了重新分析，以生产稀有类的苯丙素哌嗪生物碱（chrysosporazine）；（i）小型化24孔板培养概况（MATRIX），（ii）UPLC-DAD和UPLC-QTOF-MS/MS（GNPS）化学剖析，和;（iii）前体指导的生物合成以操纵原位生物合成性能和输出;检测两种新的黄孢嗪真菌生产者。优化的PDA固相培养曲霉的化学分析。CMB-F661产生了新的区域异构的金孢子嗪T（1）和U（2），而前体定向栽培扩大了产量，并产生了非常少量的新天然产物azachysosporazineT1(3)和U1(4)，以及新的非天然类似物新黄异孢嗪R（5）和S（6）。同样，Spiromastixsp的优化M1固相培养的化学分析。CMB-F455导致GNPS检测多种黄孢嗪和巴西，并对黄孢嗪D（7）和巴西酰胺A（8）进行了分离和结构阐明。获得新的黄孢嗪区域异构体促进了结构活性关系研究，以更好地定义黄孢嗪P-糖蛋白（P-gp）抑制药效团，其在逆转过度表达P-gp的结肠癌细胞中的多索布林抗性方面异常有效(SW600Ad300)。
