Departamento de Biotecnología, Universidad Autónoma Metropolitana-Iztapalapa, Av. Rafael Atlixco No. 186. Col. Vicentina, Iztapalapa, C.P. 09340, Mexico City, Mexico.
Curr Microbiol. 2022 Jul 7;79(8):243. doi: 10.1007/s00284-022-02935-0.
In a recent work we showed that, besides lovastatin, ROS also accumulate during the production phase in Pencillium chrysogenum and in Acremonium chrysogenum, and that these ROS regulate the biosynthesis of penicillin and cephalosporin C. In the present study, we investigated the level at which this positive regulation is exerted. Internal ROS levels were manipulated, i.e., increased or decreased, in the production phase of the respective fermentations. Penicillin production decreased by 51.2% when internal ROS concentration was diminished by 50%, while a 62% production increase was observed when ROS were increased (62%). Similarly, Cephalosporin production decreased (35%) with antioxidants and increased (54.1%) with exogenous ROS. Expression analysis of the respective pcbAB genes, encoding the non-ribosomal peptide synthetase enzymes, was performed. Results showed down regulation of these genes in fermentations with lower ROS content, and upregulation in the cultures with higher ROS content, in both species. This showed that ROS regulation of penicillin in P. chrysogenum and of cephalosporin C in A. chrysogenum, is exerted at transcriptional level. In silico analysis of the pcbAB gene promoters in both species, suggested that this regulation could be mediated by stress-response transcription factors like Yap1, SrrA and/or MsnA, and/or by the Hap complex.
在最近的一项工作中，我们表明，除了洛伐他汀，ROS 在青霉和顶头孢霉的生产阶段也会积累，并且这些 ROS 调节青霉素和头孢菌素 C 的生物合成。在本研究中，我们研究了这种正调控发挥作用的水平。在各自发酵的生产阶段，内部 ROS 水平被人为操纵，即增加或减少。当内部 ROS 浓度降低 50%时，青霉素产量下降 51.2%，而当 ROS 增加 62%时，产量增加 62%。同样，用抗氧化剂处理时，头孢菌素产量下降（35%），用外源性 ROS 处理时，产量增加（54.1%）。对编码非核糖体肽合成酶的相应 pcbAB 基因进行了表达分析。结果表明，在 ROS 含量较低的发酵液中，这些基因的表达下调，而在 ROS 含量较高的培养物中，这些基因的表达上调，在两种生物中均如此。这表明 ROS 对青霉中青霉素和顶头孢霉中头孢菌素 C 的调控是在转录水平上进行的。对两种生物的 pcbAB 基因启动子进行计算机分析表明，这种调控可能是由应激反应转录因子如 Yap1、SrrA 和/或 MsnA 以及 Hap 复合物介导的。
