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The chejuenolide biosynthetic gene cluster harboring an iterative trans-AT PKS system in Hahella chejuensis strain MB-1084.
The Journal of Antibiotics ( IF 3.3 ) Pub Date : 2018-May-01 , DOI: 10.1038/s41429-017-0023-x
Bee Gek Ng , Jae Woo Han , Dong Wan Lee , Gyung Ja Choi , Beom Seok Kim

Hahella chejuensis MB-1084 is a Gram-negative marine bacterial strain that produces unusual 17-membered carbocyclic tetraenes, chejuenolide A and B. Two fosmid clones responsible for chejuenolide production were identified from the genomic DNA library of the MB-1084 strain. Systematic inactivation of the open reading frames (ORFs) in the sequenced region defines the boundaries of the chejuenolide (che) biosynthetic gene cluster (24.9 kbp) that encodes one non-ribosomal peptide synthase (NRPS)-polyketide synthase (PKS) hybrid protein, three modular PKSs, two PKS domains, and an amine oxidase homolog. Based on the results, we found that the che PKSs have non-canonical features such as trans-AT system and insufficient number of KS domains (five KS domains) for chejuenolide production (requires eight rounds of Claisen condensation reaction). Heterologous expression of the che PKSs in the E. coli BAP1 strain provides strong evidence of the iterative characteristic of the modular PKSs. Additionally, the phylogenetic relatedness of the KS domains of che PKSs and other trans-AT PKSs was analyzed to propose a possible pathway for chejuenolide biosynthesis.

中文翻译:

化学假单胞菌生物合成基因簇具有Hahella chejuensis MB-1084菌株的反式反式AT-PKS系统。

Hahella chejuensis MB-1084是革兰氏阴性海洋细菌菌株,可产生不同寻常的17元碳环四烯,chejuenolide A和B。从MB-1084菌株的基因组DNA库中鉴定出两个负责chejuenolide产生的fosmid克隆。测序区域中开放阅读框(ORF)的系统失活定义了化学烯内酯(che)生物合成基因簇(24.9 kbp)的边界,该簇编码一种非核糖体肽合酶(NRPS)-聚酮化合物合酶(PKS)杂合蛋白,三个模块化PKS,两个PKS域和一个胺氧化酶同源物。根据结果​​,我们发现che PKS具有非经典特征,例如反式AT系统和用于生成烯菊内酯的KS域(五个KS域)数量不足(需要八轮克莱森缩合反应)。che PKS在大肠杆菌BAP1菌株中的异源表达为模块化PKS的迭代特性提供了有力的证据。此外,分析了che PKS和其他反式-AT PKS的KS结构域的系统发育相关性,为化学合成烯醇内酯提供了可能的途径。
更新日期:2018-02-27
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