Involvement of two A‐factor receptor homologues in <i>Streptomyces coelicolor</i> A3(2) in the regulation of secondary metabolism and morphogenesis

Onaka, Hiroyasu; Nakagawa, Taishiro; Horinouchi, Sueharu

doi:10.1046/j.1365-2958.1998.00832.x

Cited by 90 publications

(69 citation statements)

References 39 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data provide support for previous reports concerning the role of some of these proteins, namely, CprA and CprB from S. coelicolor, in regulating secondary metabolite biosynthesis and morphological differentiation in Streptomyces (130,134). Some bacteria are known to recognize and even metabolize the quorum-sensing signals produced by other bacteria (135).…”

Section: Gbl Signalingsupporting

confidence: 91%

The TetR Family of Regulators

Cuthbertson

Nodwell

2013

Microbiol Mol Biol Rev

469

512

View full text Add to dashboard Cite

SUMMARY The most common prokaryotic signal transduction mechanisms are the one-component systems in which a single polypeptide contains both a sensory domain and a DNA-binding domain. Among the >20 classes of one-component systems, the TetR family of regulators (TFRs) are widely associated with antibiotic resistance and the regulation of genes encoding small-molecule exporters. However, TFRs play a much broader role, controlling genes involved in metabolism, antibiotic production, quorum sensing, and many other aspects of prokaryotic physiology. There are several well-established model systems for understanding these important proteins, and structural studies have begun to unveil the mechanisms by which they bind DNA and recognize small-molecule ligands. The sequences for more than 200,000 TFRs are available in the public databases, and genomics studies are identifying their target genes. Three-dimensional structures have been solved for close to 200 TFRs. Comparison of these structures reveals a common overall architecture of nine conserved α helices. The most important open question concerning TFR biology is the nature and diversity of their ligands and how these relate to the biochemical processes under their control.

show abstract

Section: Gbl Signalingsupporting

confidence: 91%

The TetR Family of Regulators

Cuthbertson

Nodwell

2013

Microbiol Mol Biol Rev

469

512

View full text Add to dashboard Cite

show abstract

“…Multiple receptors that repress or activate different regulatory genes with a different function could generate complex functions. Onaka et al (1998) isolated two arpA homologues, cprA and cprB, from S. coelicolor A3(2), disruption of which gave different effects on antibiotic production and spore formation. Thus, it is possible that CprA and CprB function as c-butyrolactone receptors as well as ScbR in S. coelicolor A3(2), although both are basic proteins (pI 9.8 and pI 10.0), different from typical acidic c-butyrolactone receptors.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

View full text Add to dashboard Cite

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...

show abstract

“…In contrast, the CprB protein from Streptomyces coelicolor A3 (2), which is 30% identical to ArpA (284), has been purified and crystallized (264), although the ligand for CprB is still unknown. Nonetheless, CprB binds the same nucleotide sequence as does ArpA (375) and indeed CprB also serves as a negative regulator for both secondary metabolism and morphogenesis in S. coelicolor, as ArpA does in S. griseus (264,284).…”

Section: Three-dimensional Structure Of Cprbmentioning

confidence: 99%

The TetR Family of Transcriptional Repressors

Ramos

Martínez-Bueno

Molina‐Henares

et al. 2005

Microbiol Mol Biol Rev

978

1,133

View full text Add to dashboard Cite

We have developed a general profile for the proteins of the TetR family of repressors. The stretch that best defines the profile of this family is made up of 47 amino acid residues that correspond to the helix-turn-helix DNA binding motif and adjacent regions in the three-dimensional structures of TetR, QacR, CprB, and EthR, four family members for which the function and three-dimensional structure are known. We have detected a set of 2,353 nonredundant proteins belonging to this family by screening genome and protein databases with the TetR profile. Proteins of the TetR family have been found in 115 genera of gram-positive, α-, β-, and γ-proteobacteria, cyanobacteria, and archaea. The set of genes they regulate is known for 85 out of the 2,353 members of the family. These proteins are involved in the transcriptional control of multidrug efflux pumps, pathways for the biosynthesis of antibiotics, response to osmotic stress and toxic chemicals, control of catabolic pathways, differentiation processes, and pathogenicity. The regulatory network in which the family member is involved can be simple, as in TetR (i.e., TetR bound to the target operator represses tetA transcription and is released in the presence of tetracycline), or more complex, involving a series of regulatory cascades in which either the expression of the TetR family member is modulated by another regulator or the TetR family member triggers a cell response to react to environmental insults. Based on what has been learned from the cocrystals of TetR and QacR with their target operators and from their three-dimensional structures in the absence and in the presence of ligands, and based on multialignment analyses of the conserved stretch of 47 amino acids in the 2,353 TetR family members, two groups of residues have been identified. One group includes highly conserved positions involved in the proper orientation of the helix-turn-helix motif and hence seems to play a structural role. The other set of less conserved residues are involved in establishing contacts with the phosphate backbone and target bases in the operator. Information related to the TetR family of regulators has been updated in a database that can be accessed at www.bactregulators.org

show abstract

Involvement of two A‐factor receptor homologues in Streptomyces coelicolor A3(2) in the regulation of secondary metabolism and morphogenesis

Cited by 90 publications

References 39 publications

The TetR Family of Regulators

The TetR Family of Regulators

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

The TetR Family of Transcriptional Repressors

Contact Info

Product

Resources

About