Department of Bioengineering, Faculty of Engineering, İzmir Institute of Technology, Urla, İzmir, 35433, Turkey.
İzmir International Biomedicine and Genome Institute, Dokuz Eylül University, Balçova, İzmir, 35340, Turkey.
Microb Cell Fact. 2024 Jul 10;23(1):196. doi: 10.1186/s12934-024-02468-0.
Telomerase activators are promising agents for the healthy aging process and the treatment/prevention of short telomere-related and age-related diseases. The discovery of new telomerase activators and later optimizing their activities through chemical and biological transformations are crucial for the pharmaceutical sector. In our previous studies, several potent telomerase activators were discovered via fungal biotransformation, which in turn necessitated optimization of their production. It is practical to improve the production processes by implementing the design of experiment (DoE) strategy, leading to increased yield and productivity. In this study, we focused on optimizing biotransformation conditions utilizing Camarosporium laburnicola, a recently discovered filamentous fungus, to afford the target telomerase activators (E-CG-01, E-AG-01, and E-AG-02).
DoE approaches were used to optimize the microbial biotransformation processes of C. laburnicola. Nine parameters were screened by Plackett-Burman Design, and three significant parameters (biotransformation time, temperature, shaking speed) were optimized using Central Composite Design. After conducting validation experiments, we were able to further enhance the production yield of target metabolites through scale-up studies in shake flasks (55.3-fold for E-AG-01, 13-fold for E-AG-02, and 1.96-fold for E-CG-01).
Following a process optimization study using C. laburnicola, a significant increase was achieved in the production yields. Thus, the present study demonstrates a promising methodology to increase the production yield of potent telomerase activators. Furthermore, C. laburnicola is identified as a potential biocatalyst for further industrial utilization.
端粒酶激活剂是健康衰老过程和治疗/预防短端粒相关和与年龄相关疾病的有前途的药物。发现新的端粒酶激活剂,并通过化学和生物转化来优化其活性,这对制药行业至关重要。在我们之前的研究中,通过真菌生物转化发现了几种有效的端粒酶激活剂,这反过来又需要优化其生产。通过实施实验设计(DoE)策略来改进生产工艺是切实可行的,这可以提高产量和生产力。在这项研究中,我们专注于通过利用最近发现的丝状真菌卡马罗孢子菌来优化生物转化条件,以获得目标端粒酶激活剂(E-CG-01、E-AG-01 和 E-AG-02)。
使用 DoE 方法优化了卡马罗孢子菌的微生物生物转化过程。通过 Plackett-Burman 设计筛选了 9 个参数,并使用中心复合设计优化了三个显著参数(生物转化时间、温度、摇床速度)。进行验证实验后,我们能够通过摇瓶放大研究进一步提高目标代谢物的产量(E-AG-01 提高了 55.3 倍,E-AG-02 提高了 13 倍,E-CG-01 提高了 1.96 倍)。
通过使用卡马罗孢子菌进行工艺优化研究,产量得到了显著提高。因此,本研究展示了一种提高有效端粒酶激活剂产量的有前途的方法。此外,卡马罗孢子菌被鉴定为进一步工业利用的潜在生物催化剂。