Epigenetic modification is an important regulatory mechanism in the biosynthesis of secondary metabolites in Aspergillus species, which have been considered to be the treasure trove of new bioactive secondary metabolites. In this study, we reported that deletion of the epigenetic regulator gcnE, a histone acetyltransferase in the SAGA/ADA complex, resulted in the production of 12 polyketide secondary metabolites in A. niger FGSC A1279, which was previously not known to produce toxins or secondary metabolites. Chemical workup and structural elucidation by 1D/2D NMR and high resolution electrospray ionization mass (HR-ESIMS) yielded the novel compound nigerpyrone (1) and five known compounds: carbonarone A (2), pestalamide A (3), funalenone (4), aurasperone E (5), and aurasperone A (6). Based on chemical information and the literature, the biosynthetic gene clusters of funalenone (4), aurasperone E (5), and aurasperone A (6) were located on chromosomes of A. niger FGSC A1279. This study found that inactivation of GcnE activated the production of secondary metabolites in A. niger. The biosynthetic pathway for nigerpyrone and its derivatives was identified and characterized via gene knockout and complementation experiments. A biosynthetic model of this group of pyran-based fungal metabolites was proposed.

表观遗传修饰是曲霉菌种次生代谢产物生物合成中的重要调控机制，曲霉属次生代谢产物被认为是新的具有生物活性的次生代谢产物的宝库。在这项研究中，我们报道了SAGA / ADA复合物中表观遗传调节剂gcnE（组蛋白乙酰转移酶）的缺失，导致黑曲霉FGSC A1279中产生了12种聚酮类次生代谢产物，而以前不知道会产生毒素或二次生代谢产物。通过1D / 2D NMR和高分辨率电喷雾电离质量（HR-ESIMS）进行化学处理和结构解析，得到了新型化合物尼格吡隆（1）和五个已知化合物：碳酮A（2），杀虫酰胺A（3）），富乐烯酮（4），金银花香精E（5）和金银花香精A（6）。根据化学信息和文献，在黑曲霉FGSC A1279的染色体上定位了Funalenone（4），Aurasperone E（5）和Aurasperone A（6）的生物合成基因簇。这项研究发现，灭活GcnE激活了黑曲霉次生代谢产物的产生。通过基因敲除和互补实验鉴定并表征了尼格吡酮及其衍生物的生物合成途径。提出了这组以吡喃为基础的真菌代谢产物的生物合成模型。