Andrastins A−D, <i>Penicillium roqueforti</i> Metabolites Consistently Produced in Blue-Mold-Ripened Cheese

This is the first finding of andrastins in blue cheese as well as any other sample type. Here, they were produced by the secondary starter culture Penicillium roqueforti. After purification by normal-phase chromatography followed by combined reverse-phase ion-exchange chromatography, the andrastins A−D were detected by liquid chromatography combined with UV and high-resolution mass spectrometry. In 23 representative samples of European blue cheeses, andrastin A was consistently found in quantities between 0.1 and 3.7 μg/g of cheese (median 2.4 μg/g). Assuming the same molar response factors as for andrastin A, the B, C, and D analogues were present in approximately 5-, 3-, and 5−20-fold lower amounts than andrastin A, respectively. The andrastins are protein farnesyltransferase inhibitors and are capable of inhibiting the efflux of anticancer drugs from multidrug-resistant cancer cells. Thus, their presence in common blue cheese suggests a potential for a positive or negative impact on human health. Keywords: Andrastin, Penicillium roqueforti, blue-mold cheese, SPE, LC−MS, Oasis MAX本研究首次在蓝纹奶酪及其他所有样本类型中检出安德拉斯汀类化合物（andrastins）。此类化合物由次级发酵剂娄地青霉（Penicillium roqueforti）合成。经正相色谱法纯化后，再通过反相离子交换色谱法完成进一步纯化，研究人员采用液相色谱-紫外-高分辨质谱联用法，成功检出安德拉斯汀A至D四种同系物。在23份具有代表性的欧洲蓝纹奶酪样本中，安德拉斯汀A的含量稳定在0.1~3.7 μg/g奶酪之间，中位数为2.4 μg/g。若假设安德拉斯汀B、C、D同系物与安德拉斯汀A具有相同的摩尔响应因子，则其含量分别约为安德拉斯汀A的1/5、1/3以及1/5至1/20。安德拉斯汀类化合物属于蛋白法尼基转移酶抑制剂，能够抑制多药耐药癌细胞对抗癌药物的外排作用。因此，这类化合物在常见蓝纹奶酪中的存在，提示其可能对人体健康产生正向或负向影响。 关键词：安德拉斯汀（Andrastin）、娄地青霉（Penicillium roqueforti）、蓝霉奶酪、固相萃取（SPE）、液相色谱-质谱联用法（LC−MS）、Oasis MAX