A‐factor as a microbial hormone that controls cellular differentiation and secondary metabolism in <i>Streptomyces griseus</i>

Horinouchi, Sueharu; Beppu, Teruhiko

doi:10.1111/j.1365-2958.1994.tb01073.x

Cited by 170 publications

(124 citation statements)

References 32 publications

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“…Because of the operon structure of afsA-bprA, we assume that the former route is major. A bprA homologue is also located downstream of scbA, an afsA orthologue in S. coelicolor A3 (2).…”

Section: )mentioning

confidence: 99%

Hormonal control by A-factor of morphological development and secondary metabolism in Streptomyces

Horinouchi

Beppu

2007

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

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Streptomyces griseus, a well-known industrial producer of streptomycin, is a member of the genus Streptomyces, which shows a complex life cycle resembling that of fungi. Afactor, a C 13 -butyrolactone compound, was discovered as a self-regulatory factor or a bacterial hormone to induce morphological differentiation and production of secondary metabolites, including streptomycin, in this organism. Accumulating evidence has revealed an A-factortriggered signal cascade, which is composed of several key steps or components. These include: (i) AfsA catalyzing a crucial step of A-factor biosynthesis, (ii) the A-factor-specific receptor (ArpA), which acts as a transcriptional repressor for adpA, (iii) adpA, a sole target of ArpA, which encodes a global transcriptional activator AdpA, and (iv) a variety of members of the AdpA regulon, a set of the genes regulated by AdpA. A-factor is biosynthesized via five reaction steps, in which AfsA catalyzes acyl transfer between a -ketoacyl-acyl carrier protein and the hydroxyl group of dihydroxyacetone phosphate. The receptor ArpA, belonging to the TetR family, is a homodimer, each subunit of which contains a helix-turn-helix DNA-binding motif and an Afactor-binding pocket. The three-dimensional structure and conformational change upon binding A-factor are elucidated, on the basis of X-ray crystallography of CprB, an ArpA homologue. AdpA, belonging to the AraC/XylS transcriptional activator family, binds operators upstream from the promoters of a variety of the target genes and activates their transcription, thus forming the AdpA regulon. Members of the AdpA regulon includes the pathway-specific transcriptional activator gene strR that activates the whole streptomycin biosynthesis gene cluster, in addition to a number of genes that direct the multiple cellular functions required for cellular differentiation in a concerted manner. A variety of A-factor homologues as well as homologues of afsA/arpA are distributed widely among Streptomyces, indicating the significant role of this type of molecular signaling in the ecosystem and evolutional processes.

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“…Because of the operon structure of afsA-bprA, we assume that the former route is major. A bprA homologue is also located downstream of scbA, an afsA orthologue in S. coelicolor A3 (2).…”

Section: )mentioning

confidence: 99%

Hormonal control by A-factor of morphological development and secondary metabolism in Streptomyces

Horinouchi

Beppu

2007

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

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“…The synthesis of Sm is regulated by a complicated network including pleiotropic regulators (Horinouchi & Beppu, 1992) and the regulator protein, StrR, encoded by a gene of the biosynthetic gene cluster for Sm (Retzlaff e T. N E U M A N N , W. PIEPERSBERG a n d J. DISTLER a/., 1993; Retzlaff & Distler, 1995). In addition to these regulators, a hormone-like autoregulator, A-factor, controls the production of Sm in S. grisezls at the level of gene expression via a still-unknown mechanism (Horinouchi & Beppu, 1994). The induction of Sm synthesis had commonly been described as a response to nutrient limitation in the stationary growth phase (SGP), probably mediated by ppGpp (Martin, 1989 ;Demain, 1989;Ochi, 1987a, b).…”

Section: Introductionmentioning

confidence: 99%

Decision phase regulation of streptomycin production in Streptomyces griseus

1996

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The streptomycin (Sm) producer, Streptomyces griseus N2-3-11, shows medium-independent biphasic kinetics of the vegetative or exponential growth phase (EGP), reflecting an innate clock-like behaviour of growth and differentiation. The 5. griseus growth and development cycle has the following characteristics: (1) after the developmental cycle commences, it cannot be influenced b y environmental conditions; (2) the first EGP (decision phase) and its duration seem to be genetically determined, and it is also exhibited in pleiotropic mutants deficient in differentiation and antibiotic production; (3) during this early phase of growth, the decision to produce S m is established and the fixation of later production and differentiation can only be influenced by effector molecules, e.g. A-factor, during this period; (4) after the onset of the second EGP, the commitment to S m production cannot be reversed by dilution into fresh medium, nor by effector molecules; (5) the length of time of this effector-insensitive growth phase (second EGP or execution phase) can be extended by dilution into fresh medium; (6) the differentiation cycle of S. griseus is completed on entering stationary phase. The cells of 5. griseus then return to a decision-making stage and recover sensitivity to effector molecules. Evidence that this type of phasing is valid for the growth and developmental cycles of all streptomycetes is discussed.

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“…For example, a set of six amino acids initiates fruiting body formation in Myxococcus xanthus (Kaiser, 1996;Kaplan and Plamann, 1996), whereas oligopeptides activate conjugation by Enterococcus faecalis (Clewell, 1993), stimulate competence for genetic transformation and sporulation in Bacillus subtilis (Prego and Hoch, 1996;Solomon et al, 1996) and control the production of virulence factors in Staphylococcus aureus (Ji et al, 1995). In Streptomyces spp., a ␥-butyrolactone derivative controls aerial hyphae formation, sporulation and antibiotic production (Stephens, 1986;Horinouchi and Beppu, 1994).…”

Section: Introductionmentioning

confidence: 99%

Identification of 3‐hydroxypalmitic acid methyl ester as a novel autoregulator controlling virulence in Ralstonia solanacearum

Flavier

Clough

Schell

et al. 1997

Molecular Microbiology

270

197

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SummaryExpression of virulence genes in Ralstonia solanacearum, a phytopathogenic bacterium, is controlled by a complex regulatory network that integrates multiple signal inputs. Production of several virulence determinants is co-ordinately reduced by inactivation of phcB, but is restored by growth in the presence of a volatile extracellular factor (VEF) produced by wildtype strains of R. solanacearum. The VEF was purified from spent culture broth by distillation, solvent extraction, and liquid chromatography. Gas chromatography and mass spectroscopy identified 3-hydroxypalmitic acid methyl ester (3-OH PAME) as the major component in the single peak of VEF activity. Authentic 3-OH PAME and the purified VEF were active at Յ1 nM, and had nearly equivalent specific activities for stimulating the expression of eps (the biosynthetic locus for extracellular polysaccharide) in a phcB mutant. Authentic 3-OH PAME also increased the production of three virulence factors by a phcB mutant over 20-fold to wild-type levels, restored normal cell density-associated expression of eps and increased expression of eps when delivered via the vapour phase. Reanalysis of the PhcB amino acid sequence suggested that it is a small-molecule S-adenosylmethionine-dependent methyltransferase, which might catalyse synthesis of 3-OH PAME from a naturally occurring fatty acid. Biologically active concentrations of extracellular 3-OH PAME were detected before the onset of eps expression, suggesting that it is an intercellular signal that autoregulates virulence gene expression in wild-type R. solanacearum. Other than acyl-homoserine lactones, 3-OH PAME is the only endogenous fatty acid derivative shown to be an autoregulator and may be the first example of a new family of compounds that can mediate long-distance intercellular communication.

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A‐factor as a microbial hormone that controls cellular differentiation and secondary metabolism in Streptomyces griseus

Cited by 170 publications

References 32 publications

Hormonal control by A-factor of morphological development and secondary metabolism in Streptomyces

Hormonal control by A-factor of morphological development and secondary metabolism in Streptomyces

Decision phase regulation of streptomycin production in Streptomyces griseus

Identification of 3‐hydroxypalmitic acid methyl ester as a novel autoregulator controlling virulence in Ralstonia solanacearum

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