Abstract：
Phenazines are aromatic compounds with antifungal and cytotoxic activities. Phenazines incorporating phenazine 1-carboxylic acid have widespread applications in agriculture, medicine, and industry. Griseoluteic acid is a cytotoxic compound secreted by Streptomyces griseoluteus P510, displaying potential medical applications. However, the biosynthetic pathway of griseoluteic acid has not been elucidated, limiting its development and application. In this study, a conserved phenazine biosynthetic gene cluster of S. griseoluteus P510 was identified through genomic analysis. Subsequently, its was confirmed that the four essential modification enzymes SgpH, SgpI, SgpK, and SgpL convert phenazine-1,6-dicarboxylic acid into griseoluteic acid by heterologous expression in Escherichia coli. Moreover, the biosynthetic pathway of griseoluteic acid was established in Pseudomonas chlororaphis characterized by a high growth rate and synthesis efficiency of phenazines, laying the foundation for the efficient production of griseoluteic acid.
摘要：
吩嗪是具有抗真菌和细胞毒活性的芳香族化合物。含有吩嗪1-羧酸的吩嗪在农业中具有广泛的应用，医学,和工业。灰黄酸是由灰黄链霉菌P510分泌的细胞毒性化合物，显示出潜在的医学应用。然而,灰黄酸的生物合成途径尚未阐明，限制了它的开发和应用。在这项研究中,通过基因组分析，鉴定了灰叶链球菌P510的保守吩嗪生物合成基因簇。随后，证实了四种必需的修饰酶SgpH，SgpI,SgpK,和SgpL通过在大肠杆菌中的异源表达将吩嗪-1,6-二羧酸转化为灰黄酸。此外，在绿线假单胞菌中建立了灰黄酸的生物合成途径，其特征是吩嗪的高生长速率和合成效率，为灰黄酸的高效生产奠定基础。
