Department of Botany and Microbiology, Faculty of Science, Sohag University, Sohag, EG-82524, Egypt.
Department of Botany and Microbiology, Faculty of Science, Assiut University, Assiut, EG-71516, Egypt.
BMC Biotechnol. 2024 Oct 4;24(1):73. doi: 10.1186/s12896-024-00896-9.
Biotransformation of steroid compounds into therapeutic products using microorganisms offers an eco-friendly and economically sustainable approach to the pharmaceutical industry rather than a chemical synthesis way. The biotransformation efficiency of progesterone into the anticancer compound testololactone using Penicillium chrysogenum Ras3009 has been investigated. Besides, maximization of testololactone formation was achieved by studying the kinetic modelling and impact of some fermentation conditions on the biotransformation process.
The fungal strain Ras3009 was selected among twelve fungal strains as the most runner for the transformation of 81.18% of progesterone into testololactone. Ras3009 was identified phenotypically and genotypically as Penicillium chrysogenum, its 18 S rRNA nucleotide sequence was deposited in the GenBank database by the accession number OR480104. Studying the impact of fermentation conditions on biotransformation efficiency indicated a positive correlation between substrate concentration and testololactone formation until reaching the maximum velocity v. Kinetic studies revealed that v was [Formula: see text] gLhr with high accuracy, giving R of 0.977. The progesterone transformation efficiency generally increased with time, reaching a maximum of 100% at 42 h with testololactone yield (Y) 0.8700 mg/mg. Moreover, the study indicated that the enzymatic conversion by P. chrysogenum Ras3009 showed high affinity to the substrate, intracellularly expressed, and released during cell disruption, leading to higher efficiency when using whole microbial cell extract.
Fungi can be promising biocatalysts for steroid transformation into valuable chemicals and pharmaceutical compounds. The study revealed that the new fungal isolate P. chrysogenum Ras3009 possesses a great catalytic ability to convert progesterone into testololactone. Kinetic modelling analysis and optimization of the fermentation conditions lead to higher transformation efficiency and provide a better understanding of the transformation processes.
利用微生物将甾体化合物生物转化为治疗产品为制药行业提供了一种环保且经济可持续的方法，而不是采用化学合成方法。本研究考察了利用青霉（Penicillium chrysogenum） Ras3009 将孕酮生物转化为抗癌化合物睾内酯的转化效率。此外，通过研究动力学模型和一些发酵条件对生物转化过程的影响，实现了睾内酯形成的最大化。
在 12 株真菌中，选择真菌菌株 Ras3009 作为将 81.18%孕酮转化为睾内酯的最适菌株。Ras3009 在表型和基因型上均被鉴定为青霉（Penicillium chrysogenum），其 18S rRNA 核苷酸序列已在 GenBank 数据库中注册，登录号为 OR480104。研究发酵条件对生物转化效率的影响表明，底物浓度与睾内酯形成之间呈正相关，直到达到最大速度 v。动力学研究表明，v 为 [Formula: see text] gLhr，具有很高的准确性，R 为 0.977。孕酮转化率通常随时间增加，在 42 小时时达到 100%，睾内酯产率（Y）为 0.8700mg/mg。此外，研究表明，青霉（Penicillium chrysogenum） Ras3009 酶促转化对底物具有高亲和力，在细胞内表达，并在细胞破碎时释放，从而在使用全微生物细胞提取物时效率更高。
真菌可以作为甾体转化为有价值的化学物质和药物化合物的有前途的生物催化剂。本研究表明，新的真菌分离株青霉（Penicillium chrysogenum） Ras3009 具有将孕酮转化为睾内酯的巨大催化能力。动力学模型分析和发酵条件的优化提高了转化效率，并提供了对转化过程的更好理解。
