Elucidation of the Biosynthesis of Griseoluteic Acid in Streptomyces griseoluteus P510,Journal of Natural Products

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Elucidation of the Biosynthesis of Griseoluteic Acid in Streptomyces griseoluteus P510
Journal of Natural Products ( IF 3.3 ) Pub Date : 2024-06-04 , DOI: 10.1021/acs.jnatprod.4c00017
Ying Liu ₁ , Sheng-Jie Yue ₁ , Wei Wang ₁ , Hong-Bo Hu _{1,

2} , Xue-Hong Zhang _{1,

2}

Affiliation

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.

中文翻译：

灰黄链霉菌 P510 中灰黄酸生物合成的阐明

吩嗪是具有抗真菌和细胞毒活性的芳香族化合物。包含吩嗪1-羧酸的吩嗪在农业、医药和工业中具有广泛的应用。灰黄酸是由灰黄链霉菌P510 分泌的一种细胞毒性化合物，具有潜在的医学应用价值。然而灰黄酸的生物合成途径尚未阐明，限制了其开发和应用。本研究通过基因组分析鉴定了灰黄链霉菌P510 保守的吩嗪生物合成基因簇。随后，证实四种必需修饰酶SgpH、SgpI、SgpK和SgpL通过在大肠杆菌中异源表达将吩嗪-1,6-二甲酸转化为灰黄酸。此外，在绿针假单胞菌中建立了具有高生长速率和吩嗪合成效率的灰草酸生物合成途径，为灰草酸的高效生产奠定了基础。

更新日期：2024-06-04

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