title: gamma-Butyrolactone autoregulator-receptor system involved in lankacidin and lankamycin production and morphological differentiation in Streptomyces rochei.
abstract: An afsA homologue (srrX) and three gamma-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 gamma-butyrolactone receptor system in this strain. Addition of a gamma-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.
authors.affiliation: Department of Molecular Biotechnology, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Arakawa
authors.affiliation: Department of Molecular Biotechnology, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Mochizuki
authors.affiliation: Department of Molecular Biotechnology, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Molecular Biotechnology, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Noma
authors.affiliation: Department of Molecular Biotechnology, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Kinashi
mesh_terms: D015107:4-Butyrolactone / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D000898:Antibiosis; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000096:biosynthesis; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D018942:Macrolides / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D010802:Phylogeny; D010957:Plasmids; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D013302:Streptomyces / Q000235:genetics / Q000254:growth & development* / Q000648:ultrastructure
chemical_list: C037481:4-butyrolactone receptor; D001426:Bacterial Proteins; D018942:Macrolides; D011963:Receptors, GABA-A; C008250:lankacidins; D004917:Erythromycin; C100149:kujimycin B; D015107:4-Butyrolactone