洛伐他汀工业菌株土曲霉HZ01的次级代谢产物合成分析

Synthesis of secondary metabolites by lovastatin-producing strain Aspergillus terreus HZ01

摘要:

[目的]分析洛伐他汀工业生产菌株土曲霉HZ01的次级代谢产物合成能力，为后期的遗传改造、次级代谢产物及其基因簇挖掘提供指导。[方法]对洛伐他汀发酵条件下的样品进行了转录组分析，同时运用色谱分离技术及波谱学方法对主要次级代谢产物进行了分离和结构鉴定。[结果]洛伐他汀合成相关基因转录水平非常高，还有4个聚酮合酶（PKS）、6个非核糖体多肽合成酶（NRPS）和1个PKS-NRPS杂合酶基因进行了转录，其他PKS和NRPS基因都处于沉默状态。此外，从该菌的发酵产物中分离鉴定了10个主要副产物并确定了其结构。[结论]土曲霉HZ01是一株优良的洛伐他汀生产菌株，在构建次级代谢产物异源合成细胞工厂和鉴定次级代谢产物生物合成途径方面具有很好的应用潜力。

关键词:土曲霉;次级代谢产物;洛伐他汀;工业菌株;转录组

Abstract:

[Objective] The biosynthesis ability of secondary metabolites in the lovastatin-producing strain Aspergillus terreus HZ01 was analyzed, for strain improvement and genome mining of secondary metabolites through genetic engineering. [Methods] The transcriptome of Aspergillus terreus HZ01 under the condition of lovastatin fermentation was analyzed. Meanwhile, the main by-products were separated and identified by chromatographic separation and spectroscopy. [Results] The biosynthesis of lovastatin was very active, and most of other PKS and NRPS genes are silent besides of 4 PKS, 6 NRPS and 1 PKS-NRPS. In addition, 10 major by-products were isolated and identified from the cultures. [Conclusion] Aspergillus terreus HZ01 is an excellent lovastatin producing strain, which will also be a valuable chassis cell for the microbial cell factory construction and biosynthesis pathway identification.

Key words:Aspergillus terreus;secondary metabolites;lovastatin;industrial strain;transcriptome