Institute for Technical Microbiology, Department of Biotechnology, Mannheim University of Applied Sciences, Mannheim, 68163, Germany.
Center for Biotechnology, Bielefeld University, Bielefeld, 33594, Germany.
Environ Microbiol. 2020 Aug;22(8):3248-3265. doi: 10.1111/1462-2920.15066. Epub 2020 Jun 18.
The bacterium Streptomyces davaonensis synthesizes the antibiotic roseoflavin in the stationary phase of growth. The starting point for roseoflavin biosynthesis is riboflavin (vitamin B ) and four enzymes (RibCF, RosB, RosA and RosC) are necessary to convert a vitamin (riboflavin) into a potent, broad-spectrum antibiotic (roseoflavin). In S. davaonensis, seven enzymatic functions are required to synthesize the roseoflavin precursor riboflavin from the central building blocks GTP and ribulose 5-phosphate. When compared with other bacterial and in particular Streptomyces genomes the S. davaonensis genome contains an unusual high number (21) of putative riboflavin biosynthetic genes (rib genes), including a rib gene encoding an additional riboflavin synthase originating from an Archaeon. We show by complementation analyses and enzyme assays that 17 out of these 21 putative rib genes indeed encode for riboflavin biosynthetic enzymes. Biochemical analyses of selected enzymes support this finding. Transcriptome analyses show that all of the rib genes are expressed either in the exponential or in the stationary phase of growth and thus do not represent silent genes. We conclude that the Rib enzymes produced in the stationary phase represent a physiological adaptation to support roseoflavin biosynthesis.
达瓦链霉菌在生长的静止期合成抗生素玫瑰黄素。玫瑰黄素生物合成的起点是核黄素(维生素 B ),需要四种酶(RibCF、RosB、RosA 和 RosC)将维生素(核黄素)转化为有效的广谱抗生素(玫瑰黄素)。在 S. davaonensis 中,需要七个酶功能从中心构建块 GTP 和核酮糖 5-磷酸合成玫瑰黄素前体核黄素。与其他细菌,特别是链霉菌基因组相比,S. davaonensis 基因组包含异常高数量(21)的假定核黄素生物合成基因(rib 基因),包括一个编码来自古菌的额外核黄素合酶的 rib 基因。我们通过互补分析和酶分析表明,这 21 个假定的 rib 基因中的 17 个确实编码核黄素生物合成酶。对选定酶的生化分析支持这一发现。转录组分析表明,所有的 rib 基因要么在指数生长期,要么在静止期表达,因此不是沉默基因。我们得出结论,静止期产生的 Rib 酶代表了一种生理适应,以支持玫瑰黄素的生物合成。