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Identification of the Scopularide Biosynthetic Gene Cluster in Scopulariopsis brevicaulis

机译:短S鱼中cop鱼生物合成基因簇的鉴定

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摘要

Scopularide A is a promising potent anticancer lipopeptide isolated from a marine derived Scopulariopsis brevicaulis strain. The compound consists of a reduced carbon chain (3-hydroxy-methyldecanoyl) attached to five amino acids (glycine, l-valine, d-leucine, l-alanine, and l-phenylalanine). Using the newly sequenced S. brevicaulis genome we were able to identify the putative biosynthetic gene cluster using genetic information from the structurally related emericellamide A from Aspergillus nidulans and W493-B from Fusarium pseudograminearum. The scopularide A gene cluster includes a nonribosomal peptide synthetase (NRPS1), a polyketide synthase (PKS2), a CoA ligase, an acyltransferase, and a transcription factor. Homologous recombination was low in S. brevicaulis so the local transcription factor was integrated randomly under a constitutive promoter, which led to a three to four-fold increase in scopularide A production. This indirectly verifies the identity of the proposed biosynthetic gene cluster.
机译:Scopularide A是一种有前景的有效抗癌脂肽,可从海洋衍生的Scopulariopsis brevicaulis菌株中分离出来。该化合物由与五个氨基酸(甘氨酸,L-缬氨酸,D-亮氨酸,L-丙氨酸和L-苯丙氨酸)连接的还原碳链(3-羟基-甲基癸酰基)组成。使用新测序的短短链霉菌基因组,我们能够利用来自构巢曲霉的结构相关的大黄酰胺A和来自镰孢镰刀菌的W493-B的遗传信息来鉴定推定的生物合成基因簇。 scopularide A基因簇包括非核糖体肽合成酶(NRPS1),聚酮化合物合酶(PKS2),CoA连接酶,酰基转移酶和转录因子。短链葡萄球菌的同源重组很低,因此局部转录因子被随机整合在组成型启动子下,这导致scopularide A产量增加了三到四倍。这间接验证了提出的生物合成基因簇的身份。

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