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炭疽菌ES026的全基因组测序揭示了石杉碱甲可能的合成途径。

Genome sequencing of Colletotrichum gloeosporioides ES026 reveals plausible pathway of HupA.

作者信息

Xia Haiyang, Noushahi Hamza Armghan, Khan Aamir Hamid, Liu Ying, Cosoveanu Andreea, Cui Lingli, Tang Jing, Iqbal Shehzad, Shu Shaohua

机构信息

College of Plant Science and Technology, Huazhong Agricultural University, 430070, Wuhan, China.

Bio-Pharmaceuticals Institute , Taizhou University, 317000, Taizhou, China.

出版信息

Mol Biol Rep. 2022 Dec;49(12):11611-11622. doi: 10.1007/s11033-022-07850-y. Epub 2022 Sep 26.

Abstract

BACKGROUND

Colletotrichum gloeosporioides ES026, isolated as an endophytic fungal strain, was found to produce the important medicinal compound HuperzineA (HupA). In a genetic context, ES026 showed potential in elucidating the biosynthetic pathway of HupA.

METHODS AND RESULTS

The ES026 strain was sequenced using de-novo Illumina sequencing methods in this study. Assembling the cleaned data resulted in 58,594,804bp, consisting of 404 scaffolds. The G + C mol % content of this genome was 52.53%. The genome progressive-alignment with other 4 Colletotrichum strains revealed that ES026 showed closer relation with 030206, SMCG1#C and Nara gc5. More than 60 putative biosynthetic clusters were predicted with the fungal version antiSMASH4.0 program. More than 33 types I polyketide-related biosynthetic gene clusters were distributed, containing PKS and PKS-NRPS (polyketide-nonribosomal peptides) hybrid gene clusters. Another 8 NRPS biosynthetic gene clusters were distributed among the genome of ES026. The prenyltransferases, probably involved in aromatic prenyl-compounds and terpenoid biosynthesis, were analyzed using bioinformatics tools like MEGA.

CONCLUSION

We predicted a new possible biosynthetic pathway for the HupA from the pipecolic acid, based on the published HupA biosynthesis proposed pathway, the biosynthesis and pipecolic acid-derived compounds. We hypothesize that a hybrid PKS-NRPS mega-enzyme was probably involved in the biosynthesis of HupA with the pipecolic acid, the building block of rapamycin, as a HupA precursor. The rapamycin is produced from a polyketide biosynthesis pathway, and the domain incorporating the pipecolic acid is studied.

摘要

背景

胶孢炭疽菌ES026作为一种内生真菌菌株被分离出来,发现它能产生重要的药用化合物石杉碱甲(HupA)。在遗传学背景下,ES026在阐明HupA的生物合成途径方面显示出潜力。

方法与结果

本研究采用Illumina从头测序方法对ES026菌株进行测序。对清理后的数据进行组装,得到58,594,804bp,由404个支架组成。该基因组的G + C摩尔百分比含量为52.53%。与其他4种炭疽菌菌株进行基因组渐进比对显示,ES026与030206、SMCG1#C和奈良gc5的关系更为密切。使用真菌版antiSMASH4.0程序预测了60多个假定的生物合成簇。分布了33种以上与I型聚酮相关的生物合成基因簇,包括聚酮合酶(PKS)和聚酮合酶-非核糖体肽(PKS-NRPS)杂交基因簇。另外8个非核糖体肽合成酶(NRPS)生物合成基因簇分布在ES026的基因组中。使用MEGA等生物信息学工具对可能参与芳香族异戊烯基化合物和萜类生物合成的异戊烯基转移酶进行了分析。

结论

基于已发表的HupA生物合成途径、生物合成以及哌啶酸衍生化合物,我们预测了一条从哌啶酸合成HupA的新的可能生物合成途径。我们假设一种PKS-NRPS杂交巨型酶可能参与了以哌啶酸(雷帕霉素的结构单元,作为HupA的前体)合成HupA的过程。雷帕霉素由聚酮生物合成途径产生,并且对纳入哌啶酸的结构域进行了研究。

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