活性氧在深液发酵和固态发酵过程中调节土曲霉中洛伐他汀的生物合成。
Reactive oxygen species regulate lovastatin biosynthesis in Aspergillus terreus during submerged and solid-state fermentations.
作者信息
Miranda Roxana U, Gómez-Quiroz Luis E, Mendoza Mariel, Pérez-Sánchez Ailed, Fierro Francisco, Barrios-González Javier
机构信息
Departamento de Biotecnología, Universidad Autónoma Metropolitana -Iztapalapa, Av. San Rafael Atlixco 186, Col. Vicentina, Iztapalapa, 09340 México D.F., Mexico; Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana -Iztapalapa, Av. San Rafael Atlixco 186, Col. Vicentina, Iztapalapa, 09340 México D.F., Mexico.
Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana -Iztapalapa, Av. San Rafael Atlixco 186, Col. Vicentina, Iztapalapa, 09340 México D.F., Mexico.
出版信息
Fungal Biol. 2014 Dec;118(12):979-89. doi: 10.1016/j.funbio.2014.09.002. Epub 2014 Sep 28.
In a previous work we detected an important increase in reactive oxygen species (ROS) concentrations during idiophase in lovastatin fermentations. Hence, the objective of the present work was to determine if ROS contributes to the regulation of lovastatin biosynthesis. Exogenous antioxidants were used to reduce ROS accumulation. The addition of N-Acetyl-L-cysteine (NAC) decreased ROS accumulation and concurrent lovastatin production. In solid-state fermentation (SSF), the addition of 100 mM of NAC lowered ROS accumulation by 53%, together with a 79% decrease in lovastatin biosynthesis. A similarly, situation was observed in submerged fermentation (SmF). Decreased lovastatin production was due to a lower expression of the regulatory gene lovE, and gene lovF. Moreover, the addition of H2O2 to the culture caused precocious gene expression and lovastatin biosynthesis. These results indicate that ROS accumulation in idiophase contributes to the regulation of the biosynthetic genes. It was considered that Yap1 (Atyap1) could be a transcription factor linking ROS with lovastatin biosynthesis. In a Northern analysis, Aspergillus terreus yap1 gene (Atyap1) was highly expressed during trophophase but down regulated during idiophase. Conversely, expression pattern of srrA gene, suggested that SrrA could positively control lovastatin biosynthesis, and also explaining the characteristics of the biosynthesis in SSF.
在之前的一项研究中,我们检测到洛伐他汀发酵对数期活性氧(ROS)浓度显著增加。因此,本研究的目的是确定ROS是否参与洛伐他汀生物合成的调控。使用外源性抗氧化剂来减少ROS的积累。添加N-乙酰-L-半胱氨酸(NAC)可降低ROS的积累以及同时降低洛伐他汀的产量。在固态发酵(SSF)中,添加100 mM的NAC可使ROS积累降低53%,同时洛伐他汀生物合成降低79%。在深层发酵(SmF)中也观察到类似情况。洛伐他汀产量降低是由于调控基因lovE和基因lovF的表达降低。此外,向培养物中添加H2O2会导致基因过早表达和洛伐他汀生物合成。这些结果表明对数期ROS的积累有助于生物合成基因的调控。据认为,Yap1(Atyap1)可能是一个将ROS与洛伐他汀生物合成联系起来的转录因子。在Northern分析中,土曲霉yap1基因(Atyap1)在营养期高表达,但在对数期下调。相反,srrA基因的表达模式表明,SrrA可以正向控制洛伐他汀的生物合成,也解释了固态发酵中生物合成的特点。