异源生物合成聚酮化合物的研究进展

Research Progresses on Biosynthesizing Polyketides in Heterologous Hosts

聚酮是一大类具有重要生物活性的天然产物,其生物合成途径复杂多样。利用异源宿主合成聚酮化合物要比使用天然生产菌有很多优点。异源宿主的选择是异源生物合成聚酮的关键。这种宿主必须能够大量表达大分子聚酮合成酶(300 kDa或更大)且能够大规模的转译后修饰这些蛋白;还要能够形成大量的像丙二酰CoA、甲基丙二酰CoA等细胞内起始单元。随着各种技术的不断进步,异源宿主很可能成为大规模生产聚酮化合物的一个强有力平台。本文对聚酮合成酶,异源生产聚酮的优点、条件和应用都有所阐述。

Polyketides are a large family of natural products with important bioactivity. Polyketide biosynthesis pathways are diverse and complicated. The production of polyketides in heterologous hosts offers many advantages over the use of natural producers. Choosing a fit heterologous host is a key factor in biosynthesizing polyketides in heterologous hosts. The host must be able to express relatively large polykefide synthase （300 kDa or larger）, post-translationally modify these proteins, and produce adequate supplies of intracellular starter units such as malonyl-CoA and methylmalonyl-CoA. With continued improvements to these and other techniques, heterologous hosts promise to become a robust platform for large-scale polyketide production. This paper is about the polykefide synthase and the advantage, condition, application of heterologous production systems.