title: Identification of genetic variations associated with epsilon-poly-lysine biosynthesis in Streptomyces albulus ZPM by genome sequencing.
abstract: The biosynthesis of the antibiotic epsilon-poly-lysine (ε-PL) in Streptomyces albulus is performed by polylysine synthase (pls); however, the regulatory mechanism of this process is still unknown. Here, we first obtained the complete genome sequence of S. albulus ZPM, which consists of 9,784,577 bp and has a GC content of 72.2%. The genome houses 44 gene clusters for secondary metabolite biosynthesis, in which 20 gene clusters are involved in the biosynthesis of polyketides and nonribosomally synthesized peptides. High-throughput sequencing was further performed, and genetic variants were identified from pooled libraries consisting of the 30 highest-yield mutants or 30 lowest-yield mutants. More than 350 genetic variants associated with ε-PL yield have been identified. One hundred sixty-two affected proteins, from important metabolic enzymes to novel transcriptional regulators, were identified as being related to ε-PL synthesis. HrdD, one of the affected genes, is a sigma factor that shows the most sensitive response to pH change and contains a non-synonymous mutation (A132V) in mutant strains with lower ε-PL yields. Electrophoretic mobility shift assays showed that the pls gene is likely regulated by transcriptional activator HrdD. The data obtained in this study will facilitate future studies on ε-PL yield improvement and industrial bioprocess optimization.
authors.affiliation: School of Life Sciences, University of Science &Technology of China, Hefei, Anhui 230027, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Life Sciences, University of Science &Technology of China, Hefei, Anhui 230027, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Gao
authors.affiliation: School of Life Sciences, University of Science &Technology of China, Hefei, Anhui 230027, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Tang
authors.affiliation: CAS Key Laboratory of Genome Sciences &Information, Beijing institute of Genomics, CAS, 100101.
authors.forename: Songnian
authors.initials: S
authors.lastname: Hu
authors.affiliation: 1] School of Life Sciences, University of Science &Technology of China, Hefei, Anhui 230027, China [2] CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science &Technology of China, Hefei, Anhui 230027, China.
authors.forename: Qingfa
authors.initials: Q
authors.lastname: Wu
mesh_terms: D001481:Basal Metabolism / Q000235:genetics; D002874:Chromosome Mapping; D002876:Chromosomes, Bacterial; D005798:Genes, Bacterial; D014644:Genetic Variation; D016680:Genome, Bacterial; D059014:High-Throughput Nucleotide Sequencing; D005810:Multigene Family; D011107:Polylysine / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic; D064210:Secondary Metabolism / Q000235:genetics; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: D014157:Transcription Factors; D011107:Polylysine