Gene Cluster Responsible for Validamycin Biosynthesis in
            <i>Streptomyces hygroscopicus</i>
            subsp.
            <i>jinggangensis</i>
            5008

Yu, Yi; Bai, Linquan; Minagawa, Kazuyuki; Jian, Xiao‐Hong; Li, Lei; Li, Jialiang; Chen, Shuangya; Cao, E; Mahmud, Taifo; Floss, Heinz G.; Zhou, Xing; Deng, Zixin

doi:10.1128/aem.71.9.5066-5076.2005

Cited by 76 publications

(108 citation statements)

References 27 publications

(21 reference statements)

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“…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

confidence: 98%

Characterization of the tunicamycin gene cluster unveiling unique steps involved in its biosynthesis

Chen

Zhai

et al. 2010

Protein Cell

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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.

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Section: Comparative Analysis Of the (Potential) Gene Clusters For Tumentioning

confidence: 98%

Characterization of the tunicamycin gene cluster unveiling unique steps involved in its biosynthesis

Chen

Zhai

et al. 2010

Protein Cell

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“…There were lots of reports about the use of Streptomyces spp. to control RSB [2,6,21,31,43,44,50,62,65]. From the beginning of 1970s, China and Japan were all used the metabolic products validamycin (purificated from the metabolites of S. hygroscopicus var.…”

Section: Discussionmentioning

confidence: 99%

Biocontrol activities of bacteria from cowdung against the rice sheath blight pathogen

Yang

Zhang²,

YiQing

et al. 2017

J Plant Dis Prot

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To discover bacteria with potential biocontrol activity against the rice sheath blight (RSB) pathogen, Rhizoctonia solani, cowdung (CD) associated bacteria were screened for antifungal activity a dual-culture method. Five potential biocontrol bacteria were identified to species-level based on their colony morphology, physiology, biochemical characteristics, utilization of carbon sources, micromorphology and 16S rRNA sequences. The ability of two selected strains to inhibit RSB was evaluated in vivo and in vitro. The median effective concentration (EC 50 ) of crude extract from Streptomyces cochorusii strain NF0919 (NF0919) culture filtrate was 1.3 lg ml -1 , lower than the EC 50 of Jinggangmycin (a commercial antifungal agent widely used in China). At a concentration of 25.0 lg ml -1 , the crude extract completely inhibited mycelial growth of R. solani. The field biocontrol efficacy after spraying 7 days in 2013 and in 2014 was 78.4 and 98.1% with crude extract from NF0919 culture filtrate and 71.1 and 94.2% with fresh cells of Bacillus amyloliquefaciens strain SB177 (SB177). Results from the 2-year field experiment suggested that the crude extract from NF0919 culture filtrate or fresh cells of SB177 provided better disease control than other fungicides (Jinggangmycin and/ or Kresoxim-methyl). S. cochorusii strain NF0919 and B. amyloliquefaciens strain SB177 have good potential for field application and commercial use against the RSB pathogen.

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“…Moreover, as the whole genome of S. hygroscopicus 5008 has been sequenced (Wu et al 2012), it is clear that S. hygroscopicus 5008 contains a total of 29 secondary gene clusters including the val gene cluster, which ranges from valN to valQ and covers all the genes required for VAL-A biosynthesis. Eight genes controlled by three operonsvalABC, valKLMN, and valG-are necessary and sufficient for in vivo VAL-A biosynthesis (Yu et al 2005). In addition, ValG, a glucosyltransferase, was found to be responsible for the transfer of an activated glucose to validoxylamine A (VO), which is the last step in the VAL-A biosynthesis Fan et al 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Due to its high efficiency, safety to both animal and human health, and the possibility of economic production from agro-industrial by-products or feedstock (e.g., soybean meal, peanut cake, corn powder, and rice powder), VAL-A has been widely used in East Asia, especially China, for controlling sheath blight disease of crops and dumping-off disease in vegetable seedlings (Fan et al 2013;Wei et al 2011;Zhou et al 2012). Moreover, VAL-A can be converted to valienamine, which is an important precursor for the production of voglibose, an alpha-glucosidase inhibitor in the treatment of diabetes (Fan et al 2013;Yu et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Enhanced production of validamycin A in Streptomyces hygroscopicus 5008 by engineering validamycin biosynthetic gene cluster

Zhou

Kim

Zhong

2014

Appl Microbiol Biotechnol

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Validamycin A (VAL-A) is a widely used antifungal antibiotic for the treatment of sheath blight disease of rice and other plants. It can be produced from agro-industrial by-products by Streptomyces hygroscopicus 5008. To enhance its production titer, in this work, the entire val gene cluster was amplified in tandem in S. hygroscopicus 5008 by integrating the zouA-mediated DNA amplification system into between the two boundaries of val gene cluster, resulting in multiple copies (mainly three to five) of the val gene cluster. The genetic stability of the amplified copies was confirmed by Southern blot and fermentation experiments. In shake flask fermentation, the recombinant strain (TC03) led to a 34% enhancement of VAL-A production titer compared to that of the wild-type strain, while the accumulation of intermediate validoxylamine A was decreased in TC03. Additionally, both the structural gene transcription levels and the ValG enzyme activity were significantly increased in TC03. This work demonstrated that the amplification of the val gene cluster was an efficient strategy to enhance VAL-A production by S. hygroscopicus 5008, and the information obtained would be helpful for engineering other interesting antibiotic biosynthesis by gene cluster amplification.

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Gene Cluster Responsible for Validamycin Biosynthesis in Streptomyces hygroscopicus subsp. jinggangensis 5008

Cited by 76 publications

References 27 publications

Characterization of the tunicamycin gene cluster unveiling unique steps involved in its biosynthesis

Characterization of the tunicamycin gene cluster unveiling unique steps involved in its biosynthesis

Biocontrol activities of bacteria from cowdung against the rice sheath blight pathogen

Enhanced production of validamycin A in Streptomyces hygroscopicus 5008 by engineering validamycin biosynthetic gene cluster

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