Comparative genomics of Alexander Fleming's original Penicillium isolate (IMI 15378) reveals sequence divergence of penicillin synthesis genes.
Comparative genomics of Alexander Fleming's original Penicillium isolate (IMI 15378) reveals sequence divergence of penicillin synthesis genes.
复制标题
DOI：
10.1038/s41598-020-72584-5
复制
发表时间：
2020-09-24
影响因子：
4.6
通讯作者：
Barraclough TG
中科院分区：
文献类型：
--
作者：
Pathak A;Nowell RW;Wilson CG;Ryan MJ;Barraclough TG
抗生素最初来源于野生生物，因此了解这些化合物如何在不同谱系中进化可能有助于设计新的抗菌药物。我们报告了亚历山大·弗莱明发现青霉素后的原始真菌分离物的基因组序列草图，现在分类为青霉（1923）（IMI 15378）。我们比较了两种“高产”工业菌株P. rubens和密切相关的物种P. nalgiovense的基因组结构和参与青霉素合成的基因。生产青霉素G的主要效应基因（pcbAB、pcbC和penDE）在弗莱明菌株和两种工业菌株之间显示出氨基酸差异，而一组调控基因则是保守的。青霉素N效应基因cefD1和cefD2也有同源性，后者在氨基酸上与工业菌株存在差异。在所有三种鲁本假单胞菌菌株中，草案组件包含青霉素途径基因的几个部分复制，在不同程度上，我们假设这可能参与了途径的调节。这两个工业菌株在所有效应基因和调控基因的序列上是相同的，但在pcbAB-pcbC-penDE复合体的重复和调控基因片段的部分重复上存在差异。我们得出结论，野生环境下的进化包括效应基因的序列变化和基因复制，而人类介导的突变和人工选择导致青霉素途径基因的复制。
Antibiotics were derived originally from wild organisms and therefore understanding how these compounds evolve among different lineages might help with the design of new antimicrobial drugs. We report the draft genome sequence of Alexander Fleming’s original fungal isolate behind the discovery of penicillin, now classified as Penicillium rubens Biourge (1923) (IMI 15378). We compare the structure of the genome and genes involved in penicillin synthesis with those in two ‘high producing’ industrial strains of P. rubens and the closely related species P. nalgiovense. The main effector genes for producing penicillin G (pcbAB, pcbC and penDE) show amino acid divergence between the Fleming strain and both industrial strains, whereas a suite of regulatory genes are conserved. Homologs of penicillin N effector genes cefD1 and cefD2 were also found and the latter displayed amino acid divergence between the Fleming strain and industrial strains. The draft assemblies contain several partial duplications of penicillin-pathway genes in all three P. rubens strains, to differing degrees, which we hypothesise might be involved in regulation of the pathway. The two industrial strains are identical in sequence across all effector and regulatory genes but differ in duplication of the pcbAB–pcbC–penDE complex and partial duplication of fragments of regulatory genes. We conclude that evolution in the wild encompassed both sequence changes of the effector genes and gene duplication, whereas human-mediated changes through mutagenesis and artificial selection led to duplication of the penicillin pathway genes.
登录
查看更多内容
影响因子：
5.6
作者：
Caruso, ML;Litzka, O;Brakhage, AA
通讯作者：
Brakhage, AA
影响因子：
--
作者：
Barreiro C;Martín JF;García-Estrada C
通讯作者：
García-Estrada C
影响因子：
9.1
作者：
Houbraken J;Frisvad JC;Seifert KA;Overy DP;Tuthill DM;Valdez JG;Samson RA
通讯作者：
Samson RA
影响因子：
4.2
作者：
García-Estrada C;Vaca I;Ullán RV;van den Berg MA;Bovenberg RA;Martín JF
通讯作者：
Martín JF
影响因子：
1.7
作者：
Bankevich, Anton;Nurk, Sergey;Pevzner, Pavel A.
通讯作者：
Pevzner, Pavel A.