Arakawa Kenji, Mochizuki Susumu, Yamada Kohei, Noma Takenori, Kinashi Haruyasu
Department of Molecular Biotechnology, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
Microbiology (Reading). 2007 Jun;153(Pt 6):1817-1827. doi: 10.1099/mic.0.2006/002170-0.
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.
在罗氏链霉菌7434AN4（两种聚酮类抗生素兰卡杀菌素和兰卡霉素的产生菌）的巨大线性质粒pSLA2-L上编码着一个afsA同源物（srrX）和三个γ-丁内酯受体基因同源物（srrA、srrB和srrC）。基因破坏株的构建及其表型研究表明，srrX和srrA在该菌株中构成了一个γ-丁内酯受体系统。向srrX缺陷型突变体中添加γ-丁内酯组分可恢复兰卡杀菌素和兰卡霉素的产生，这表明SrrX蛋白对于此过程并非必需。除了对抗生素产生有积极作用外，srrX对形态分化有消极作用。受体基因srrA逆转了srrX的这两种作用，而第二个受体基因同源物srrC在孢子形成中仅具有积极功能。此外，第三个同源物srrB的破坏极大地增加了兰卡杀菌素和兰卡霉素的产生。电子显微镜分析表明，气生菌丝体的形成在srrA和srrC突变体的不同阶段停止。总体而言，这些结果表明，srrX、srrA、srrB和srrC构成了罗氏链霉菌中抗生素产生和形态分化的复杂调控系统。
