New knowledge about the biosynthesis of lovastatin and its production by fermentation ofAspergillus terreus

被引:31
作者
Barrios-Gonzalez, Javier [1 ]
Perez-Sanchez, Ailed [1 ]
Bibian, Maria Esmeralda [1 ]
机构
[1] Univ Autonoma Metropolitana Iztapalapa, Dept Biotecnol, Ave San Rafael Atlixco 186, Mexico City 09340, DF, Mexico
关键词
Lovastatin biosynthesis; New regulatory mechanisms; ROS regulation; Quorum sensing type molecules; Support stimuli; Strain improvement and process optimization; SOLID-STATE FERMENTATION; SECONDARY METABOLITE PRODUCTION; TO-CELL COMMUNICATION; ASPERGILLUS-TERREUS; TRANSCRIPTION FACTOR; ACREMONIUM-CHRYSOGENUM; PELLET MORPHOLOGY; GENE-EXPRESSION; MOLECULAR-BASIS; C BIOSYNTHESIS;
D O I
10.1007/s00253-020-10871-x
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Lovastatin, and its semisynthetic derivative simvastatine, has great medical and economic importance, besides great potential for other uses. In the last years, a deeper and more complex view of secondary metabolism regulation has emerged, with the incorporation of cluster-specific and global transcription factors, and their relation to signaling cascades, as well as the new level of epigenetic regulation. Recently, a new mechanism, which regulates lovastatin biosynthesis, at transcriptional level, has been discovered: reactive oxygen species (ROS) regulation; also new unexpected environmental stimuli have been identified, which induce the synthesis of lovastatin, like quorum sensing-type molecules and support stimuli. The present review describes this new panorama and uses this information, together with the knowledge on lovastatin biosynthesis and genomics, as the foundation to analyze literature on optimization of fermentation parameters and medium composition, and also to fully understand new strategies for strain genetic improvement. This new knowledge has been applied to the development of more effective culture media, with the addition of molecules like butyrolactone I, oxylipins, and spermidine, or with addition of ROS-generating molecules to increase internal ROS levels in the cell. It has also been applied to the development of new strategies to generate overproducing strains ofAspergillus terreus, including engineering of the cluster-specific transcription factor (lovE), global transcription factors like the ones implicated in ROS regulation (or even mitochondrial alternative respirationaoxgen), or the global regulator LaeA. Moreover, there is potential to apply some of these findings to the development of novel unconventional production systems.
引用
收藏
页码:8979 / 8998
页数:20
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