Decision phase regulation of streptomycin production in Streptomyces griseus

Neumann, Thomas; Piepersberg, Wolfgang; Distler, Jürgen

doi:10.1099/13500872-142-8-1953

Cited by 43 publications

(41 citation statements)

References 22 publications

(14 reference statements)

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“…SgiA begins to be produced at or just before the decision point when A-factor at a critical concentration switches the cell physiology from vegetative growth to differentiation conditions. The decision point is in the middle of the exponential growth phase (25), at which point the A-factor concentration reaches a critical level (1). Therefore, SgiA functions during and after the second exponential growth phase after the decision point.…”

Section: Discussionmentioning

confidence: 99%

Control of the Streptomyces Subtilisin Inhibitor Gene by AdpA in the A-Factor Regulatory Cascade in Streptomyces griseus

et al. 2006

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AdpA in the A-factor regulatory cascade in Streptomyces griseus activates a number of genes required for secondary metabolism and morphological differentiation, forming an AdpA regulon. The Streptomyces subtilisin inhibitor (SSI) gene, sgiA, in S. griseus was transcribed in response to AdpA, showing that sgiA is a member of the AdpA regulon. AdpA bound a single site upstream of the sgiA promoter at approximately position ؊70 with respect to its transcriptional start point. Mutational analysis of the AdpA-binding site showed that the AdpA-binding site was essential for transcriptional activation. Mutants in which sgiA was disrupted had higher trypsin, chymotrypsin, metalloendopeptidase, and total protease activities than the wild-type strain, which showed that SgiA modulated the activities of these extracellularly produced proteases. Because a number of genes encoding chymotrypsins, trypsins, and metalloendopeptidases, most of which are SSI-sensitive proteases, are also under the control of AdpA, the A-factor regulatory cascade was thought to play a crucial role in modulating the extracellular protease activities by triggering simultaneous production of the proteases and their inhibitor at a specific timing during growth. Mutants in which sgiA was disrupted grew normally and formed aerial hyphae and spores with the same time course as the wild-type strain. However, exogenous addition of purified SgiA to substrate mycelium grown on agar medium resulted in a delay in aerial mycelium formation, indicating that SgiA is involved in aerial hypha formation in conjunction with proteases.

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Section: Discussionmentioning

confidence: 99%

Control of the Streptomyces Subtilisin Inhibitor Gene by AdpA in the A-Factor Regulatory Cascade in Streptomyces griseus

et al. 2006

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“…Since A-factor switches over the cell physiology from the vegetative growth to the differentiation conditions, these proteases begin to be produced at or just before the decision point. The decision point is at the middle of the exponential growth phase (20), at which point A-factor is accumulated in the cell to reach a critical concentration (1). Therefore, these proteases function during the second exponential growth phase after the decision point.…”

Section: Control Of Extracellular Proteases By A-factor Via Adpamentioning

confidence: 99%

“…A-factor is gradually accumulated in a growth-dependent manner, with its maximum quantity, about 25 ng/ml, at or near the decision point (1). The decision point is at the middle of the exponential growth phase (20). When the concentration of A-factor reaches a critical level, it binds ArpA, which has bound the promoter of adpA, and dissociates the ArpA from the DNA, thus inducing the transcription of adpA (7,22).…”

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confidence: 99%

Three Chymotrypsin Genes Are Members of the AdpA Regulon in the A-Factor Regulatory Cascade in Streptomyces griseus

et al. 2005

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AdpA is a key transcriptional activator in the A-factor regulatory cascade in Streptomyces griseus, activating a number of genes required for secondary metabolism and morphological differentiation. Of the five chymotrypsin-type serine protease genes, sprA, sprB, and sprD were transcribed in response to AdpA, showing that these protease genes are members of the AdpA regulon. These proteases were predicted to play the same physiological role, since these protease genes were transcribed in a similar time course during growth and the matured enzymes showed high end-to-end similarity to one another. AdpA bound two sites upstream of the sprA promoter approximately at positions ؊375 and ؊50 with respect to the transcriptional start point of sprA. Mutational analysis of the AdpA-binding sites showed that both AdpA-binding sites were essential for transcriptional activation. AdpA bound a single site at position ؊50 in front of the sprB promoter and greatly enhanced the transcription of sprB. The AdpA-binding site at position ؊40 was essential for transcription of sprD, although there was an additional AdpA-binding site at position ؊180. Most chymotrypsin activity excreted by S. griseus was attributed to SprA and SprB, because mutant ⌬sprAB, having a deletion in both sprA and sprB, lost almost all chymotrypsin activity, as did mutant ⌬adpA. Even the double mutant ⌬sprAB and triple mutant ⌬sprABD grew normally and developed aerial hyphae and spores over the same time course as the wild-type strain.A-factor (2-isocapryloyl-3R-hydroxymethyl-␥-butyrolactone) is a chemical signaling molecule, or a microbial hormone, that triggers secondary metabolism and cell differentiation in Streptomyces griseus (7,8). We have revealed the A-factor regulatory cascade, through which production of almost all the secondary metabolites produced by S. griseus and formation of aerial mycelium and spores are triggered. A-factor is gradually accumulated in a growth-dependent manner, with its maximum quantity, about 25 ng/ml, at or near the decision point (1). The decision point is at the middle of the exponential growth phase (20). When the concentration of A-factor reaches a critical level, it binds ArpA, which has bound the promoter of adpA, and dissociates the ArpA from the DNA, thus inducing the transcription of adpA (7,22). The transcriptional factor AdpA activates a number of genes required for secondary metabolism and morphological differentiation. Members of the AdpA regulon include strR, the pathwayspecific transcriptional activator for streptomycin biosynthesis (30); an open reading frame encoding a probable pathwayspecific regulator for a polyketide compound (35); adsA encoding an extracytoplasmic function sigma factor of RNA polymerase essential for aerial mycelium formation (32); ssgA encoding a small acidic protein essential for spore septum formation (33); and amfR encoding a regulatory protein essential for aerial mycelium formation (34). In addition to these genes, sgmA encoding a metalloendopeptidase (12) and sprT and sprU, both e...

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“…Its rapid identification across the whole of the actinomycete clade, including mycobacteria and streptomycetes, with implications for clinical and ecological isolation (250), was the result of genomic studies, and the identification of multiple rpf genes in Mycobacterium tuberculosis and Streptomyces coelicolor was the direct result of the availability of whole-genome sequences. The whole area of stress response, signaling, and global regulatory mechanisms is now being dissected in organisms like S. coelicolor (309,344,356,486) and has important implications for growth and antibiotic expression, affecting isolation and screening strategies for natural products.…”

Section: Genomicsmentioning

confidence: 99%

Search and Discovery Strategies for Biotechnology: the Paradigm Shift

Bull

Ward

Goodfellow

2000

Microbiol Mol Biol Rev

411

247

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SUMMARY Profound changes are occurring in the strategies that biotechnology-based industries are deploying in the search for exploitable biology and to discover new products and develop new or improved processes. The advances that have been made in the past decade in areas such as combinatorial chemistry, combinatorial biosynthesis, metabolic pathway engineering, gene shuffling, and directed evolution of proteins have caused some companies to consider withdrawing from natural product screening. In this review we examine the paradigm shift from traditional biology to bioinformatics that is revolutionizing exploitable biology. We conclude that the reinvigorated means of detecting novel organisms, novel chemical structures, and novel biocatalytic activities will ensure that natural products will continue to be a primary resource for biotechnology. The paradigm shift has been driven by a convergence of complementary technologies, exemplified by DNA sequencing and amplification, genome sequencing and annotation, proteome analysis, and phenotypic inventorying, resulting in the establishment of huge databases that can be mined in order to generate useful knowledge such as the identity and characterization of organisms and the identity of biotechnology targets. Concurrently there have been major advances in understanding the extent of microbial diversity, how uncultured organisms might be grown, and how expression of the metabolic potential of microorganisms can be maximized. The integration of information from complementary databases presents a significant challenge. Such integration should facilitate answers to complex questions involving sequence, biochemical, physiological, taxonomic, and ecological information of the sort posed in exploitable biology. The paradigm shift which we discuss is not absolute in the sense that it will replace established microbiology; rather, it reinforces our view that innovative microbiology is essential for releasing the potential of microbial diversity for biotechnology penetration throughout industry. Various of these issues are considered with reference to deep-sea microbiology and biotechnology.

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Decision phase regulation of streptomycin production in Streptomyces griseus

Cited by 43 publications

References 22 publications

Control of the Streptomyces Subtilisin Inhibitor Gene by AdpA in the A-Factor Regulatory Cascade in Streptomyces griseus

Control of the Streptomyces Subtilisin Inhibitor Gene by AdpA in the A-Factor Regulatory Cascade in Streptomyces griseus

Three Chymotrypsin Genes Are Members of the AdpA Regulon in the A-Factor Regulatory Cascade in Streptomyces griseus

Search and Discovery Strategies for Biotechnology: the Paradigm Shift

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