The pleitropic regulator AdpAch is required for natamycin biosynthesis and morphological differentiation in Streptomyces chattanoogensis

Du, Yi‐Ling; Li, Shanzhen; Zhou, Zhan; Chen, Shi-Fei; Wu, Fan; Li, Yongquan

doi:10.1099/mic.0.046607-0

Cited by 46 publications

(68 citation statements)

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“…Our analysis showed that many components in the A-factor signaling cascade are conserved in the five Streptomyces genomes, including at least seven gene families functioning in a chronological order (strep 1890, strep 2366, strep 3567, strep4078, strep2310, strep1012, and strep8592) [26]: strep1890 contains an A-factor receptor ArpA, which can block the expression of AdpA (strep3567) during the growth of vegetative mycelium. Upon the activation of A-factor biosynthesis by strep2366, A-factor is accumulated, which will release the expression of AdpA (strep3567), an ECF sigma factor that can trigger the downstream effector proteins that are essential for morphological differentiation (strep4078, strep2310, and strep1012) and secondary metabolism (strep8592) [47,48]. The remaining three secondary metabolite clusters with multiple composite genes are for the biosynthesis of 5-hydroxyectoine (strep3082-3085), desferrioxamine (strep3559-3562), and hopene (strep5306-5310), which are the common natural products of streptomycetes.…”

Section: Resultsmentioning

confidence: 99%

Genome plasticity and systems evolution in Streptomyces

Zhou

et al. 2012

BMC Bioinformatics

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BackgroundStreptomycetes are filamentous soil-dwelling bacteria. They are best known as the producers of a great variety of natural products such as antibiotics, antifungals, antiparasitics, and anticancer agents and the decomposers of organic substances for carbon recycling. They are also model organisms for the studies of gene regulatory networks, morphological differentiation, and stress response. The availability of sets of genomes from closely related Streptomyces strains makes it possible to assess the mechanisms underlying genome plasticity and systems adaptation.ResultsWe present the results of a comprehensive analysis of the genomes of five Streptomyces species with distinct phenotypes. These streptomycetes have a pan-genome comprised of 17,362 orthologous families which includes 3,096 components in the core genome, 5,066 components in the dispensable genome, and 9,200 components that are uniquely present in only one species. The core genome makes up about 33%-45% of each genome repertoire. It contains important genes for Streptomyces biology including those involved in gene regulation, secretion, secondary metabolism and morphological differentiation. Abundant duplicate genes have been identified, with 4%-11% of the whole genomes composed of lineage-specific expansions (LSEs), suggesting that frequent gene duplication or lateral gene transfer events play a role in shaping the genome diversification within this genus. Two patterns of expansion, single gene expansion and chromosome block expansion are observed, representing different scales of duplication.ConclusionsOur results provide a catalog of genome components and their potential functional roles in gene regulatory networks and metabolic networks. The core genome components reveal the minimum requirement for streptomycetes to sustain a successful lifecycle in the soil environment, reflecting the effects of both genome evolution and environmental stress acting upon the expressed phenotypes. A better understanding of the LSE gene families will, on the other hand, bring a wealth of new insights into the mechanisms underlying strain-specific phenotypes, such as the production of novel antibiotics, pathogenesis, and adaptive response to environmental challenges.

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Section: Resultsmentioning

confidence: 99%

Genome plasticity and systems evolution in Streptomyces

Zhou

et al. 2012

BMC Bioinformatics

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“…Bacterial strains and plasmids used in the present study are listed in Table S1 in the supplemental material. S. chattanoogensis strains were normally maintained on YMG agar for spore preparation (9). The media (MSF, SMMS, and YEME) used for examination of morphological development and antibiotic production were prepared according to standard procedures (16).…”

Section: Methodsmentioning

confidence: 99%

“…were carried out according to standard procedures (16,29). E. coli-S. chattanoogensis conjugation and flask fermentation of S. chattanoogensis strains were performed as described previously (9).…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, it is also used to treat fungal infections, such as fungal keratitis. The biosynthetic gene clusters of NTM have been cloned in S. natalensis and S. chattanoogensis (2,9). Here, we reported the characterization of a GBL system of S. chattanoogensis, which consists of two GBL synthases ScgA and ScgX, a GBL receptor ScgR, and a yet-to-be-identified GBL molecule CHB.…”

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Gamma-Butyrolactone Regulatory System of Streptomyces chattanoogensis Links Nutrient Utilization, Metabolism, and Development

Shen

et al. 2011

Appl Environ Microbiol

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Gamma-butyrolactones (GBLs) produced by several Streptomyces species have been shown to serve as quorum-sensing signaling molecules for activating antibiotic production. The GBL system of Streptomyces chattanoogensis L10, a producer of antifungal agent natamycin, consists of three genes: scgA, scgX, and scgR. Both scgA and scgX contribute to GBL production, while scgR encodes a GBL receptor. ⌬scgA and ⌬scgX mutants of S. chattanoogensis behaved identically: they had a growth defect in submerged cultures and delayed or abolished the morphological differentiation and secondary metabolites production on solid medium. ScgR could bind to the promoter region of scgA and repress its transcription. Moreover, scgA seems also to be controlled by a GBL-mediated negative-feedback system. Hence, it is apparent that GBL biosynthesis is tightly controlled to ensure the correct timing for metabolic switch. An additional direct ScgR-target gene gbdA was identified by genomic SELEX and transcriptional analysis. Comparative proteomic analysis between L10 and its ⌬scgA mutant revealed that the GBL system affects the expression of more than 50 proteins, including enzymes involved in carbon uptake system, primary metabolism, and stress response, we thus conclude that scgR-scgA-scgX constitute a novel GBL regulatory system involved in nutrient utilization, triggering adaptive responses, and finally dictating the switch from primary to secondary metabolism. Quorum sensing (QS) is a cell-cell communication processin which bacteria use the production and detection of extracellular chemicals called autoinducers to monitor cell population density and synchronize community behavior through regulation of their gene expression in response to changes in cell density. Acyl homoserine lactones (AHLs) are a major class of autoinducers used by Gram-negative proteobacteria for intraspecies quorum sensing (23) and has been studied intensively over the past decade. Streptomyces, probably as well as its related genera, use ␥-butyrolactones (2,3-di-substituted-␥-butyrolactones) as autoinducers, the chemical structure of which is similar to that of AHLs except for the carbon side chain (31). In addition, other signal molecules, such as PI factor [2,3-diamino-2,3-bis(hydroxymethyl)-1,4-butanediol] and AHFCAs (2-alkyl-4-hydroxymethylfuran-3-carboxylic acids), have been described to play a similar role to that of GBLs in Streptomyces (6, 26).Streptomycetes are Gram-positive soil bacteria that undergo a developmental program that leads to sporulating aerial hyphae. They are also characterized by a complex secondary metabolism, which makes them the largest antibiotic-producing genus, producing over two-thirds of the clinically used antibiotics of natural origin. The ␥-butyrolactone (GBL) system of Streptomyces, typically consisting of a GBL synthase and a cognate receptor, is drawing more attention because of its close association with production of several antibiotics (31). Currently, there are four such systems with a known GBL and receptor, including the ...

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“…、纳塔尔链霉菌(Streptomyces natalensis) [3] 和恰塔努加链霉菌 (Streptomyces chatanoogensis) [4] 发酵生产。目前我国主要利用褐黄孢链霉菌 se surface methodology.…”

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High Efficient Fermentation of Natamycin with Streptomyces Gilvosporeus HBJ591

宋慧婷¹,

邓锐²,

江正兵³

2012

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Based on the study of sugar supplement process, high efficient fermentation with Streptomyces gilvosporeus HBJ591 was carried out via the optimization of the fermentation medium. When the reducing sugar concentration in the fermenter was 2.5%, the synthetic course of natamycin was extended effectively. Response surface method was used to optimize the fermention medium of HBJ591, then fed-batch fermentation was carried out in 16 L fermenter, the natamycin fermentation level reached 15.7 g/L, and the highest yield was 4.8 times higher than the original process.

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The pleitropic regulator AdpAch is required for natamycin biosynthesis and morphological differentiation in Streptomyces chattanoogensis

Cited by 46 publications

References 43 publications

Genome plasticity and systems evolution in Streptomyces

Genome plasticity and systems evolution in Streptomyces

Gamma-Butyrolactone Regulatory System of Streptomyces chattanoogensis Links Nutrient Utilization, Metabolism, and Development

High Efficient Fermentation of Natamycin with Streptomyces Gilvosporeus HBJ591

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