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Unraveling the biosynthesis of penicillenols by genome mining polyketide synthase and nonribosomal peptide synthetase gene clusters in Penicillium citrinum
AIChE Journal ( IF 3.7 ) Pub Date : 2022-08-22 , DOI: 10.1002/aic.17885
Qiuyue Nie 1 , Shuqi Guo 1 , Xue Gao 1, 2, 3
Affiliation  

Penicillenols belong to the family of tetramic acids with anticancer and antibacterial activities. Here, we report the discovery of the biosynthetic gene cluster (pnc) for penicillenol A1 and E in Penicillium citrinum ATCC9849 by genome mining. We discover the pnc cluster based on the results of gene deletions in P. citrinum and gene cluster heterologous expression in Aspergillus nidulans. We also propose the assembly line of the polyketide synthase module in PncA with the reduction by PncB provides a highly reduce polyketide chain to be further linked with an l-threonine molecule and released from PncA to produce penicillenol E. Further formation of penicillenol A1 requires the N-methylation of tetramic acid group by PncC. Our work deepens the understanding of the biosynthetic logic for N-methylated tetramic acids and contributes to the discovery of new penicillenols by genome mining.

中文翻译:

通过基因组挖掘聚酮合成酶和非核糖体肽合成酶基因簇揭示青霉烯醇的生物合成

Penicillenols 属于四环酸家族,具有抗癌和抗菌活性。在这里,我们报告了通过基因组挖掘在Penicillium citrinum ATCC9849中发现青霉烯醇A 1和 E的生物合成基因簇 ( pnc )。我们根据P. citrinum基因缺失和Aspergillus nidulans基因簇异源表达的结果发现了pnc簇。我们还提出了 PncA 中聚酮化合物合酶模块的装配线,通过 PncB 的还原提供了一个高度还原的聚酮化合物链,可以进一步与l-苏氨酸分子并从PncA中释放出来产生青霉烯醇E。青霉烯醇A 1的进一步形成需要PncC对四氨基酸基团进行N-甲基化。我们的工作加深了对N-甲基化四环酸生物合成逻辑的理解,并有助于通过基因组挖掘发现新的青霉酚。
更新日期:2022-08-22
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