Sigma factor WhiGch positively regulates natamycin production in Streptomyces chattanoogensis L10

Liu, Shuiping; Yu, Ping; Yuan, Peipei; Zhou, Zhenxing; Bu, Qing-Ting; Mao, Xu‐Ming; Li, Yongquan

doi:10.1007/s00253-014-6307-1

Cited by 27 publications

(16 citation statements)

References 39 publications

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“…It is generally uncommon for global/pleiotropic regulators to directly control structural genes involved in antibiotic biosynthesis; however, similar phenomena have been observed in other Streptomyces species. For instance, WhiG from S. chattanoogensis L10, an industrial natamycin producer, controls natamycin production as well as spore development44. It directly activates natamycin production by binding to the promoters of biosynthetic genes scnC and scnD .…”

Section: Discussionmentioning

confidence: 99%

SAV742, a Novel AraC-Family Regulator from Streptomyces avermitilis, Controls Avermectin Biosynthesis, Cell Growth and Development

Sun

Zhu

Chen

et al. 2016

Sci Rep

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Avermectins are useful anthelmintic antibiotics produced by Streptomyces avermitilis. We demonstrated that a novel AraC-family transcriptional regulator in this species, SAV742, is a global regulator that negatively controls avermectin biosynthesis and cell growth, but positively controls morphological differentiation. Deletion of its gene, sav_742, increased avermectin production and dry cell weight, but caused delayed formation of aerial hyphae and spores. SAV742 directly inhibited avermectin production by repressing transcription of ave structural genes, and also directly regulated its own gene (sav_742) and adjacent gene sig8 (sav_741). The precise SAV742-binding site on its own promoter region was determined by DNase I footprinting assay coupled with site-directed DNA mutagenesis, and 5-nt inverted repeats (GCCGA-n10/n12-TCGGC) were found to be essential for SAV742 binding. Similar 5-nt inverted repeats separated by 3, 10 or 15 nt were found in the promoter regions of target ave genes and sig8. The SAV742 regulon was predicted based on bioinformatic analysis. Twenty-six new SAV742 targets were identified and experimentally confirmed, including genes involved in primary metabolism, secondary metabolism and development. Our findings indicate that SAV742 plays crucial roles in not only avermectin biosynthesis but also coordination of complex physiological processes in S. avermitilis.

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Section: Discussionmentioning

confidence: 99%

SAV742, a Novel AraC-Family Regulator from Streptomyces avermitilis, Controls Avermectin Biosynthesis, Cell Growth and Development

Sun

Zhu

Chen

et al. 2016

Sci Rep

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“…In S. coelicolor , σ B (Cho et al, 2001; Lee et al, 2004b) and σ K (Mao et al, 2009) are involved in regulation of ACT and RED biosynthesis, although the regulatory mechanisms are unclear. In Streptomyces chattanoogensis L10, alternative σ factor WhiG ch promotes natamycin biosynthesis by directly activating two structural genes, scnC and scnD (Liu S. P. et al, 2015). In the present study, we characterized alternative σ factor σ 8 in S. avermitilis , and demonstrated that it indirectly represses avermectin production through its effects on expression of CSR gene aveR and structural gene aveA1 .…”

Section: Discussionmentioning

confidence: 99%

An Alternative σ Factor, σ8, Controls Avermectin Production and Multiple Stress Responses in Streptomyces avermitilis

et al. 2017

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Alternative σ factors in bacteria redirect RNA polymerase to recognize alternative promoters, thereby facilitating coordinated gene expression necessary for adaptive responses. The gene sig8 (sav_741) in Streptomyces avermitilis encodes an alternative σ factor, σ8, highly homologous to σB in Streptomyces coelicolor. Studies reported here demonstrate that σ8 is an important regulator of both avermectin production and stress responses in S. avermitilis. σ8 inhibited avermectin production by indirectly repressing expression of cluster-situated activator gene aveR, and by directly initiating transcription of its downstream gene sav_742, which encodes a direct repressor of ave structural genes. σ8 had no effect on cell growth or morphological differentiation under normal growth conditions. Growth of a sig8-deletion mutant was less than that of wild-type strain on YMS plates following treatment with heat, H2O2, diamide, NaCl, or KCl. sig8 transcription was strongly induced by these environmental stresses, indicating response by σ8 itself. A series of σ8-dependent genes responsive to heat, oxidative and osmotic stress were identified by EMSAs, qRT-PCR and in vitro transcription experiments. These findings indicate that σ8 plays an important role in mediating protective responses to various stress conditions by activating transcription of its target genes. Six σ8-binding promoter sequences were determined and consensus binding sequence BGVNVH-N15-GSNNHH (B: C, T or G, V: A, C or G, S: C or G, H: A, C or T, N: any nucleotide) was identified, leading to prediction of the σ8 regulon. The list consists of 940 putative σ8 target genes, assignable to 17 functional groups, suggesting the wide range of cellular functions controlled by σ8 in S. avermitilis.

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“…Other inter-species differences were previously noted between S. coelicolor and S. griseus 78 . A different kind of surprise concerning the WhiG sigma was the discovery in Streptomyces chattanoogensis that it can bind to target promoters in the absence of RNA polymerase core enzyme, including some in the gene cluster for natamycin production: binding was either to typical WhiG-binding sites or to CGTCA repeat elements, and was needed for gene activation 79 .…”

Section: New Perspectives In Growth and Development Of Streptomycesmentioning

confidence: 99%

Recent advances in understanding Streptomyces

2016

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About 2,500 papers dated 2014–2016 were recovered by searching the PubMed database for Streptomyces, which are the richest known source of antibiotics. This review integrates around 100 of these papers in sections dealing with evolution, ecology, pathogenicity, growth and development, stress responses and secondary metabolism, gene expression, and technical advances. Genomic approaches have greatly accelerated progress. For example, it has been definitively shown that interspecies recombination of conserved genes has occurred during evolution, in addition to exchanges of some of the tens of thousands of non-conserved accessory genes. The closeness of the association of Streptomyces with plants, fungi, and insects has become clear and is reflected in the importance of regulators of cellulose and chitin utilisation in overall Streptomyces biology. Interestingly, endogenous cellulose-like glycans are also proving important in hyphal growth and in the clumping that affects industrial fermentations. Nucleotide secondary messengers, including cyclic di-GMP, have been shown to provide key input into developmental processes such as germination and reproductive growth, while late morphological changes during sporulation involve control by phosphorylation. The discovery that nitric oxide is produced endogenously puts a new face on speculative models in which regulatory Wbl proteins (peculiar to actinobacteria) respond to nitric oxide produced in stressful physiological transitions. Some dramatic insights have come from a new model system for Streptomyces developmental biology, Streptomyces venezuelae, including molecular evidence of very close interplay in each of two pairs of regulatory proteins. An extra dimension has been added to the many complexities of the regulation of secondary metabolism by findings of regulatory crosstalk within and between pathways, and even between species, mediated by end products. Among many outcomes from the application of chromosome immunoprecipitation sequencing (ChIP-seq) analysis and other methods based on “next-generation sequencing” has been the finding that 21% of Streptomyces mRNA species lack leader sequences and conventional ribosome binding sites. Further technical advances now emerging should lead to continued acceleration of knowledge, and more effective exploitation, of these astonishing and critically important organisms.

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Sigma factor WhiGch positively regulates natamycin production in Streptomyces chattanoogensis L10

Cited by 27 publications

References 39 publications

SAV742, a Novel AraC-Family Regulator from Streptomyces avermitilis, Controls Avermectin Biosynthesis, Cell Growth and Development

SAV742, a Novel AraC-Family Regulator from Streptomyces avermitilis, Controls Avermectin Biosynthesis, Cell Growth and Development

An Alternative σ Factor, σ8, Controls Avermectin Production and Multiple Stress Responses in Streptomyces avermitilis

Recent advances in understanding Streptomyces

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