Deciphering the streamlined genome of Streptomyces xiamenensis 318 as the producer of the anti-fibrotic drug candidate xiamenmycin

• Published in: Scientific reports Vol. 6; no. 1; p. 18977
• Main Authors: Xu, Min-Juan, Wang, Jia-Hua, Bu, Xu-Liang, Yu, He-Lin, Li, Peng, Ou, Hong-Yu, He, Ying, Xu, Fang-Di, Hu, Xiao-Yan, Zhu, Xiao-Mei, Ao, Ping, Xu, Jun
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 08.01.2016
• Subjects: Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Benzopyrans - isolation & purification; Biosynthesis; Chromosome Mapping; DNA sequencing; Gene clusters; Gene Expression Regulation, Bacterial; Genome, Bacterial; Genomes; Genomic Islands; High-Throughput Nucleotide Sequencing; Lactams - isolation & purification; Lactams - metabolism; Metabolic Networks and Pathways - genetics; Metabolism; Metabolites; Multigene Family; Nucleotide sequence; Secondary metabolites; Streptomyces - enzymology; Streptomyces - genetics; Threonine - analogs & derivatives; Threonine - biosynthesis; Threonine - isolation & purification
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep18977

Streptomyces xiamenensis 318, a moderate halophile isolated from a mangrove sediment, produces the anti-fibrotic compound xiamenmycin. The whole genome sequence of strain 318 was obtained through long-read single-molecule real-time (SMRT) sequencing, high-throughput Illumina HiSeq and 454 pyrosequencing technologies. The assembled genome comprises a linear chromosome as a single contig of 5,961,401-bp, which is considerably smaller than other reported complete genomes of the genus Streptomyces. Based on the antiSMASH pipeline, a total of 21 gene clusters were predicted to be involved in secondary metabolism. The gene cluster responsible for the biosynthesis of xiamenmycin resides in a strain-specific 61,387-bp genomic island belonging to the left-arm region. A core metabolic network consisting of 104 reactions that supports xiamenmycin biosynthesis was constructed to illustrate the necessary precursors derived from the central metabolic pathway. In accordance with the finding of a putative ikarugamycin gene cluster in the genome, the targeted chemical profiling of polycyclic tetramate macrolactams (PTMs) resulted in the identification of ikarugamycin. A successful genome mining for bioactive molecules with different skeletons suggests that the naturally minimized genome of S. xiamenensis 318 could be used as a blueprint for constructing a chassis cell with versatile biosynthetic capabilities for the production of secondary metabolites.