真菌芳香聚酮化合物的合成生物学研究进展

Advances in Synthetic Biology of Fungal Aromatic Polyketides

真菌芳香聚酮化合物是由真菌非还原聚酮合酶(NR-PKSs)催化形成的具有广泛生物活性的一类天然产物。大部分内源真菌菌株存在难培养、致病性或产率低等问题,从根本上限制了真菌芳香聚酮化合物的开发和应用。随着合成生物学和代谢工程的发展,很多具有生物活性的聚酮产物实现了在工业微生物(如酿酒酵母、构巢曲霉等)中的异源生产,相关研究逐渐成为热点。从合成途径解析与挖掘、底盘细胞的构建与改造等方面综述了近年来真菌芳香聚酮化合物的合成生物学研究进展,为未来真菌芳香聚酮化合物人工代谢途径的高效构建和实现工业化生产奠定基础。

Fungal aromatic polyketides are a class of natural products with a wide range of bio-activite,which catalyzed by fungal non-reducing polyketide synthase(NR-PKSs).Some aromatic polyketide producting strains have problems such as difficulty in cultivation,pathogenicity,or low yield,which fundamentally limit the development and application of fungal aromatic polyketides.With the development of synthetic biology and metabolic engineering,more and more polyketides with biological activity have realized the heterogeneous production of industrial microorganisms(such as Saccharomyces cerevisiae and Aspergillus nidulans,etc.),and related research have gradually become hot spots.The research progress of the synthetic biology of fungal aromatic polyketides in recent years is reviewed from the analysis and mining of biosynthetic pathways,the construction and optimization of chassis cells,etc.,which lays the foundation for the efficient synthesis of artificial metabolic pathways of aromatic polyketides and industrial production in the future.