Effect of A‐factor on the growth of asporogenous mutants of <i>Streptomyces griseus</i>, not producing this factor

Khokhlov, A. S.; Anisova, L. N.; Tovarova, I I; Kleiner, E. M.; Коваленко, И. В.; Krasilnikova, O. I.; Kornitskaya, E. Ya.; Pliner, S. A.

doi:10.1002/jobm.19730130803

Cited by 68 publications

(27 citation statements)

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“…A-factor induces streptomycin production. 11) We therefore examined the eŠects of pamamycin-607 and A-factor on secondary metabolite production by antibacterial activity with S. aureus. Distinct increases or decreases in antibiotic activity occurred in 5 strains among 18 strains (Table 3).…”

Section: Production Of Pamamycin-607 By Streptomyces Strainsmentioning

confidence: 99%

“…A-factor induces both morphological diŠerentiation and streptomycin production in S. griseus. 11,12) The receptor protein of A-factor, ArpA, is the repressor that binds the promoter region of the transcriptional factor, adpA. 13) When the concentration of A-factor increases at a late stage of growth, A-factor binds the DNA-bound ArpA and releases ArpA from the DNA, thus activating the transcription of adpA.…”

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confidence: 99%

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Relationship between Response to and Production of the Aerial Mycelium-inducing Substances Pamamycin-607 and A-factor

Hashimoto

Kondo

Kozone

et al. 2003

Bioscience, Biotechnology, and Biochemistry

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Section: Production Of Pamamycin-607 By Streptomyces Strainsmentioning

confidence: 99%

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confidence: 99%

Relationship between Response to and Production of the Aerial Mycelium-inducing Substances Pamamycin-607 and A-factor

Hashimoto

Kondo

Kozone

et al. 2003

Bioscience, Biotechnology, and Biochemistry

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“…In particular, the A-factor regulatory system has been extensively studied and its hierarchical regulatory cascade was proposed (Ohnishi et al, 1999). afsA is involved in the synthesis of A-factor, a c-butyrolactone autoregulator (Hara & Beppu, 1982;Khokhlov et al, 1973), which binds to ArpA, a repressor-type receptor, and releases it from the promoter region of adpA. The derepressed and produced AdpA protein, a global transcriptional activator, in turn binds to the promoter of strR, a positive regulator gene for streptomycin biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

γ-Butyrolactone autoregulator-receptor system involved in lankacidin and lankamycin production and morphological differentiation in Streptomyces rochei

et al. 2007

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An afsA homologue (srrX) and three c-butyrolactone receptor gene homologues (srrA, srrB and srrC) are coded on the giant linear plasmid pSLA2-L in Streptomyces rochei 7434AN4, a producer of two polyketide antibiotics, lankacidin and lankamycin. Construction of gene disruptants and their phenotypic study revealed that srrX and srrA make a c-butyrolactone receptor system in this strain. Addition of a c-butyrolactone fraction to an srrX-deficient mutant restored the production of lankacidin and lankamycin, indicating that the SrrX protein is not necessary for this event. In addition to a positive effect on antibiotic production, srrX showed a negative effect on morphological differentiation. The receptor gene srrA reversed both effects of srrX, while the second receptor gene homologue srrC had only a positive function in spore formation. Furthermore, disruption of the third homologue srrB greatly increased the production of lankacidin and lankamycin. Electron microscopic analysis showed that aerial mycelium formation stopped at a different stage in the srrA and srrC mutants. Overall, these results indicated that srrX, srrA, srrB and srrC constitute a complex regulatory system for antibiotic production and morphological differentiation in S. rochei. INTRODUCTIONThe filamentous Gram-positive soil bacteria of the genus Streptomyces are characterized by three distinct properties: linear chromosome, complex morphological differentiation and ability to produce varieties of secondary metabolites including antibiotics. Antibiotic biosynthetic genes in Streptomyces species usually form a condensed gene cluster on the chromosome. However, several giant linear plasmids encoding an antibiotic gene cluster(s) have been isolated: SCP1 in Streptomyces coelicolor A3(2) carries the biosynthetic gene cluster for methylenomycin (Bentley et al., 2004;Chater & Bruton, 1985;Kinashi et al., 1987;Redenbach et al., 1998), pPZG103 in Streptomyces rimosus has that for oxytetracycline (Gravius et al., 1994; Pandza et al., 1998) and pSLA2-L in Streptomyces rochei has those for lankacidin and lankamycin (Arakawa et al., 2005(Arakawa et al., , 2006Mochizuki et al., 2003;Suwa et al., 2000).S. rochei strain 7434AN4 contains three large linear plasmids (pSLA2-L, -M and -S) (Kinashi et al., 1994) and produces two structurally unrelated polyketide antibiotics, the 17-membered macrocyclic lankacidin and the 14-membered macrolide lankamycin (Fig. 1a). We have been studying the function of the largest linear plasmid pSLA2-L in antibiotic production, and finally determined its 210 614 bp nucleotide sequence (Mochizuki et al., 2003). It was revealed that pSLA2-L contains an unusually condensed gene organization for secondary metabolism (Fig. 1b); two type I PKS gene clusters for lankacidin (lkc, orf4-orf18) and lankamycin (lkm, orf24-orf53), a cryptic type II PKS gene cluster (roc, orf62-orf70) and a carotenoid biosynthetic gene cluster (crt, orf104-orf110). In addition, many regulatory genes were identified on pSLA2-L, including all the homologues in t...

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“…Pioneering studies to understand the ␥-butyrolactone signaling system have been carried out with Streptomyces griseus, a streptomycin producer. In this bacterium, the ␥-butyrolactone known as A-factor (2-isocapryloyl-3R-hydroxymethyl-␥-butyrolactone) (6,12) is synthesized by the afsA gene product (7,10). In the absence of A-factor, the A-factor receptor protein, ArpA (23), binds to the promoter region of the global transcriptional activator gene, adpA, and represses its transcription (22).…”

mentioning

confidence: 99%

γ-Butyrolactone-Dependent Expression of theStreptomycesAntibiotic Regulatory Protein GenesrrYPlays a Central Role in the Regulatory Cascade Leading to Lankacidin and Lankamycin Production inStreptomyces rochei

Yamamoto

Arakawa

et al. 2008

J Bacteriol

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Our previous studies revealed that the srrX and srrA genes carried on the large linear plasmid pSLA2-L constitute a ␥-butyrolactone-receptor system in Streptomyces rochei. Extensive transcriptional analysis has now showed that the Streptomyces antibiotic regulatory protein gene srrY, which is also carried on pSLA2-L, is a target of the receptor/repressor SrrA and plays a central role in lankacidin and lankamycin production. The srrY gene was expressed in a growth-dependent manner, slightly preceding antibiotic production. The expression of srrY was undetectable in the srrX mutant but was restored in the srrX srrA double mutant. In addition, SrrA was bound specifically to the promoter region of srrY, and this binding was prevented by the addition of the S. rochei ␥-butyrolactone fraction, while the W119A mutant receptor SrrA was kept bound even in the presence of S. rochei ␥-butyrolactone. Furthermore, the introduction of an intact srrY gene under the control of a foreign promoter into the srrX or srrA(W119A) mutant restored antibiotic production. All of these results confirmed the signaling pathway from srrX through srrA to srrY, leading to lankacidin and lankamycin production.

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Effect of A‐factor on the growth of asporogenous mutants of Streptomyces griseus, not producing this factor

Cited by 68 publications

References 11 publications

Relationship between Response to and Production of the Aerial Mycelium-inducing Substances Pamamycin-607 and A-factor

Relationship between Response to and Production of the Aerial Mycelium-inducing Substances Pamamycin-607 and A-factor

γ-Butyrolactone autoregulator-receptor system involved in lankacidin and lankamycin production and morphological differentiation in Streptomyces rochei

γ-Butyrolactone-Dependent Expression of theStreptomycesAntibiotic Regulatory Protein GenesrrYPlays a Central Role in the Regulatory Cascade Leading to Lankacidin and Lankamycin Production inStreptomyces rochei

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