Micro-Pollutant Research Centre (MPRC), Faculty of Civil Engineering & Built Environment, Universiti Tun Hussein Onn Malaysia, Parit Raja, 86400 Batu Pahat, Malaysia.
Center for Diagnostic, Therapeutic and Investigative Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
Molecules. 2021 Apr 25;26(9):2510. doi: 10.3390/molecules26092510.
The present research aimed to enhance the pharmaceutically active compounds' (PhACs') productivity from SUK 25 in submerged fermentation using response surface methodology (RSM) as a tool for optimization. Besides, the characteristics and mechanism of PhACs against methicillin-resistant were determined. Further, the techno-economic analysis of PhACs production was estimated. The independent factors include the following: incubation time, pH, temperature, shaker rotation speed, the concentration of glucose, mannitol, and asparagine, although the responses were the dry weight of crude extracts, minimum inhibitory concentration, and inhibition zone and were determined by RSM. The PhACs were characterized using GC-MS and FTIR, while the mechanism of action was determined using gene ontology extracted from DNA microarray data. The results revealed that the best operating parameters for the dry mass crude extracts production were 8.20 mg/L, the minimum inhibitory concentrations (MIC) value was 8.00 µg/mL, and an inhibition zone of 17.60 mm was determined after 12 days, pH 7, temperature 28 °C, shaker rotation speed 120 rpm, 1 g glucose /L, 3 g mannitol/L, and 0.5 g asparagine/L with R coefficient value of 0.70. The GC-MS and FTIR spectra confirmed the presence of 21 PhACs, and several functional groups were detected. The gene ontology revealed that 485 genes were upregulated and nine genes were downregulated. The specific and annual operation cost of the production of PhACs was U.S. Dollar (U.S.D) 48.61 per 100 mg compared to U.S.D 164.3/100 mg of the market price, indicating that it is economically cheaper than that at the market price.
本研究旨在利用响应面法（RSM）作为优化工具，提高亚硫酸盐（SUK 25）在液体发酵中药物活性化合物（PhACs）的产量。此外，还确定了 PhACs 对耐甲氧西林金黄色葡萄球菌的特性和作用机制。进一步，对 PhACs 生产的技术经济分析进行了评估。独立因素包括：培养时间、pH 值、温度、摇床转速、葡萄糖、甘露醇和天冬酰胺的浓度，尽管响应是通过 RSM 确定的粗提物干重、最小抑菌浓度和抑菌圈。PhACs 采用 GC-MS 和 FTIR 进行表征，而作用机制则采用 DNA 微阵列数据提取的基因本体确定。结果表明，粗提物干重生产的最佳操作参数为 8.20mg/L，最小抑菌浓度（MIC）值为 8.00μg/mL，12 天后确定抑菌圈为 17.60mm，pH 值为 7，温度为 28°C，摇床转速为 120rpm，1g/L 葡萄糖，3g/L 甘露醇和 0.5g/L 天冬酰胺，R 系数值为 0.70。GC-MS 和 FTIR 图谱证实存在 21 种 PhACs，检测到几个功能基团。基因本体揭示了 485 个基因上调和 9 个基因下调。PhACs 生产的特定和年度运营成本为每 100mg 48.61 美元（USD），而市场价格为每 100mg USD164.3，表明其比市场价格更经济实惠。
