Genetic localization and heterologous expression of validamycin biosynthetic gene cluster isolated from Streptomyces hygroscopicus var. limoneus KCCM 11405 (IFO 12704)
“…Interestingly, the tunL homolog was missing in the potential gene cluster of A. mirum DSM 43827, which may partly account for the lack of tunicamycin production by this strain. In addition, the sequence homologies among the three gene clusters were relatively low (Table S3) compared with the gene clusters of validamycin, which was produced by several Streptomyces, for example (Yu et al, 2005;Bai et al, 2006;Jian et al, 2006;Singh et al, 2006). Remarkably, there are no discernable nucleotide homologies in two tunicamycin gene clusters of S. chartreusis and S. clavuligerus (Table S3).…”
Section: Comparative Analysis Of the (Potential) Gene Clusters For Tumentioning
Tunicamycin, a potent reversible translocase I inhibitor, is produced by several Actinomycetes species. The tunicamycin structure is highly unusual, and contains an 11-carbon dialdose sugar and an α, β-1″,11′-glycosidic linkage. Here we report the identification of a gene cluster essential for tunicamycin biosynthesis by high-throughput heterologous expression (HHE) strategy combined with a bioassay. Introduction of the genes into heterologous non-producing Streptomyces hosts results in production of tunicamycin by these strains, demonstrating the role of the genes for the biosynthesis of tunicamycins. Gene disruption experiments coupled with bioinformatic analysis revealed that the tunicamycin gene cluster is minimally composed of 12 genes (tunAtunL). Amongst these is a putative radical SAM enzyme (Tun B) with a potentially unique role in biosynthetic carbon-carbon bond formation. Hence, a seven-step novel pathway is proposed for tunicamycin biosynthesis. Moreover, two gene clusters for the potential biosynthesis of tunicamycin-like antibiotics were also identified in Streptomyces clavuligerus ATCC 27064 and Actinosynnema mirums DSM 43827. These data provide clarification of the novel mechanisms for tunicamycin biosynthesis, and for the generation of new-designer tunicamycin analogs with selective/enhanced bioactivity via combinatorial biosynthesis strategies.
“…Interestingly, the tunL homolog was missing in the potential gene cluster of A. mirum DSM 43827, which may partly account for the lack of tunicamycin production by this strain. In addition, the sequence homologies among the three gene clusters were relatively low (Table S3) compared with the gene clusters of validamycin, which was produced by several Streptomyces, for example (Yu et al, 2005;Bai et al, 2006;Jian et al, 2006;Singh et al, 2006). Remarkably, there are no discernable nucleotide homologies in two tunicamycin gene clusters of S. chartreusis and S. clavuligerus (Table S3).…”
Section: Comparative Analysis Of the (Potential) Gene Clusters For Tumentioning
Tunicamycin, a potent reversible translocase I inhibitor, is produced by several Actinomycetes species. The tunicamycin structure is highly unusual, and contains an 11-carbon dialdose sugar and an α, β-1″,11′-glycosidic linkage. Here we report the identification of a gene cluster essential for tunicamycin biosynthesis by high-throughput heterologous expression (HHE) strategy combined with a bioassay. Introduction of the genes into heterologous non-producing Streptomyces hosts results in production of tunicamycin by these strains, demonstrating the role of the genes for the biosynthesis of tunicamycins. Gene disruption experiments coupled with bioinformatic analysis revealed that the tunicamycin gene cluster is minimally composed of 12 genes (tunAtunL). Amongst these is a putative radical SAM enzyme (Tun B) with a potentially unique role in biosynthetic carbon-carbon bond formation. Hence, a seven-step novel pathway is proposed for tunicamycin biosynthesis. Moreover, two gene clusters for the potential biosynthesis of tunicamycin-like antibiotics were also identified in Streptomyces clavuligerus ATCC 27064 and Actinosynnema mirums DSM 43827. These data provide clarification of the novel mechanisms for tunicamycin biosynthesis, and for the generation of new-designer tunicamycin analogs with selective/enhanced bioactivity via combinatorial biosynthesis strategies.
“…limoneus, and later from S. hygroscopicus var. yingchengensis 10-22 [10][11][12] . In the 45-kb se-ARTICLES MICROBIOLOGY quenced region of S. hygroscopicus 5008, 27 genes were deduced and 8 required structure genes for VAL biosynthesis were defined through heterologous expression (Figure 1(a)).…”
“…limoneus and acarbose from Actinoplanes sp. 17) However, these actinomycetes are not suitable for use in the food industry. In contrast, Bacillus spp.…”
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