Role of nsdA in negative regulation of antibiotic production and morphological differentiation in Streptomyces bingchengensis

Wang, Xiangjing; Guo, Suo-Lian; Guo, Wei; Xi, Di; Xiang, Wensheng

doi:10.1038/ja.2009.33

Cited by 20 publications

(14 citation statements)

References 35 publications

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“…4G): up to 28-fold for activators of aerial mycelium differentiation ( bldB , bldC , bldN , bldM ); up to 147-fold for transcripts involved in the formation of hydrophobic covers ( sapA , chpC, chpD, chpE, chpH, ramA, ramC, ramS ); up to 3.2-fold for sporulation regulatory genes ( wblA , whiG , whiH ); and 73-fold for ndsA , a gene affecting antibiotic production [40]. WhiJ , a repressor of sporulation [41], was the only exception, as it was up-regulated during the non-sporulating phase (MI).…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic Analysis of Liquid Non-Sporulating Streptomyces coelicolor Cultures Demonstrates the Existence of a Complex Differentiation Comparable to That Occurring in Solid Sporulating Cultures

et al. 2014

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Streptomyces species produce many clinically relevant secondary metabolites and exhibit a complex development that includes hyphal differentiation and sporulation in solid cultures. Industrial fermentations are usually performed in liquid cultures, conditions in which Streptomyces strains generally do not sporulate, and it was traditionally assumed that no differentiation took place. The aim of this work was to compare the transcriptomes of S. coelicolor growing in liquid and solid cultures, deepening the knowledge of Streptomyces differentiation. Microarrays demonstrated that gene expression in liquid and solid cultures were comparable and data indicated that physiological differentiation was similar for both conditions. Eighty-six percent of all transcripts showed similar abundances in liquid and solid cultures, such as those involved in the biosynthesis of actinorhodin (actVA, actII-4) and undecylprodigiosin (redF); activation of secondary metabolism (absR1, ndsA); genes regulating hydrophobic cover formation (aerial mycelium) (bldB, bldC, bldM, bldN, sapA, chpC, chpD, chpE, chpH, ramA, ramC, ramS); and even some genes regulating early stages of sporulation (wblA, whiG, whiH, whiJ). The two most important differences between transcriptomes from liquid and solid cultures were: first, genes related to secondary metabolite biosynthesis (CDA, CPK, coelichelin, desferrioxamine clusters) were highly up-regulated in liquid but not in solid cultures; and second, genes involved in the final stages of hydrophobic cover/spore maturation (chpF, rdlA, whiE, sfr) were up-regulated in solid but not in liquid cultures. New information was also provided for several non-characterized genes differentially expressed in liquid and solid cultures which might be regulating, at least in part, the metabolic and developmental differences observed between liquid and solid cultures.

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Section: Resultsmentioning

confidence: 99%

Transcriptomic Analysis of Liquid Non-Sporulating Streptomyces coelicolor Cultures Demonstrates the Existence of a Complex Differentiation Comparable to That Occurring in Solid Sporulating Cultures

et al. 2014

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“…NsdA is not obviously related to proteins of known structure or function, but streptomycetes usually have several paralogues. In Streptomyces bingchengensis, NsdA represses production of the macrolide milbemycin and a polyether, nangchangmycin (189). The effects of NsdA are thus applied to a wide range of antibiotic biosynthetic pathways.…”

Section: How Does Bldd Regulate Development and Antibiotic Production?mentioning

confidence: 99%

“…More than 150 other direct targets of BldD have been determined, leading to the delineation of a refined consensus target site, 5=-nTnCnC(A/T)GnGTnAn-3= (171). Among a relatively high representation of regulatory genes, the target genes include the following: adpA and bldA; bldC, encoding a small protein with a single MerR-like domain that is needed for development and antibiotic production (187); and nsdA, which encodes an apparent repressor of ACT, RED, and CDA production and of differentiation (188,189). Orthologues of BldD and BldC are found in many actinobacteria, including some that are morphologically simple, have small genomes, and are not known as antibiotic producers, while NsdA orthologues are present in all streptomycetes and their closest relatives but are absent from other actinomycetes.…”

Section: How Does Bldd Regulate Development and Antibiotic Production?mentioning

confidence: 99%

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

Liu

Chater

Chandra

et al. 2013

Microbiol Mol Biol Rev

592

536

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SUMMARY Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor , the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes.

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“…Another insecticidal antibiotic, the polyether ionophore nanchangmycin, can also be produced by S. bingchenggensis (8). Furthermore, two novel cyclic pentapeptides, bingchamides A and B, have also been isolated from this strain (9). Considering the fertility of the secondary metabolites produced by S. bingchenggensis, its genome sequence should provide fundamental understanding of the biosynthesis of these compounds and facilitate the bioengineering efforts involving this species.…”

mentioning

confidence: 99%

Genome Sequence of the Milbemycin-Producing Bacterium Streptomyces bingchenggensis

et al. 2010

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Streptomyces bingchenggensis is a soil-dwelling bacterium producing the commercially important anthelmintic macrolide milbemycins. Besides milbemycins, the insecticidal polyether antibiotic nanchangmycin and some other antibiotics have also been isolated from this strain. Here we report the complete genome sequence of S. bingchenggensis. The availability of the genome sequence of S. bingchenggensis should enable us to understand the biosynthesis of these structurally intricate antibiotics better and facilitate rational improvement of this strain to increase their titers.

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Role of nsdA in negative regulation of antibiotic production and morphological differentiation in Streptomyces bingchengensis

Cited by 20 publications

References 35 publications

Transcriptomic Analysis of Liquid Non-Sporulating Streptomyces coelicolor Cultures Demonstrates the Existence of a Complex Differentiation Comparable to That Occurring in Solid Sporulating Cultures

Transcriptomic Analysis of Liquid Non-Sporulating Streptomyces coelicolor Cultures Demonstrates the Existence of a Complex Differentiation Comparable to That Occurring in Solid Sporulating Cultures

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

Genome Sequence of the Milbemycin-Producing Bacterium Streptomyces bingchenggensis

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