title: Deciphering the streamlined genome of Streptomyces xiamenensis 318 as the producer of the anti-fibrotic drug candidate xiamenmycin.
abstract: 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.
authors.affiliation: Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Centre for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Min-Juan
authors.initials: MJ
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.|Institute of Oceanology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Jia-Hua
authors.initials: JH
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.|Institute of Oceanology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Xu-Liang
authors.initials: XL
authors.lastname: Bu
authors.affiliation: Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Centre for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: He-Lin
authors.initials: HL
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Ou
authors.affiliation: State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.affiliation: State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Fang-Di
authors.initials: FD
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.|Institute of Oceanology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Hu
authors.affiliation: Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Centre for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Zhu
authors.affiliation: Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Centre for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ao
authors.affiliation: State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.|Institute of Oceanology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001578:Benzopyrans / Q000302:isolation & purification; D002874:Chromosome Mapping; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D044404:Genomic Islands; D059014:High-Throughput Nucleotide Sequencing; D007769:Lactams / Q000302:isolation & purification / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics; D005810:Multigene Family; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics*; D013912:Threonine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000302:isolation & purification
chemical_list: D001426:Bacterial Proteins; D001578:Benzopyrans; D007769:Lactams; C582113:N-((3,4-dihydro-3-hydroxy-2-methyl-2-(4'-methyl-3'-pentenyl)-2H-1-benzopyran-6-yl)carbonyl)threonine; D013912:Threonine; C074292:ikarugamycin