Carbon Source Optimization for Industrial Streptomyces sp. Fermentation

Antibiotic resistance represents one of the most critical challenges that society must face. Many bacteria develop this resistance through the production of the enzyme ß-lactamase, which makes ineffective the largely used ß-lactam antibiotics. However, certain molecules derived from bacterial fermentation can counteract this enzyme, thus mitigating antibiotic resistance. One of the most important belongs to the class of inhibitors for ß-lactamase, which is produced by the gram-positive bacterial genus Streptomyces. The industrial process for ß-lactamase inhibitors production is generally well known and established but intrinsically variable. A better understanding of the factors that influence growth and production could help to increase yield and productivity. Within this context, nutrients consumption plays a crucial role. The optimization of nutrients concentrations, indeed, could not only help to optimize the fermentation performances but also to decrease the process costs, avoiding raw materials waste. In Streptomyces industrial cultivation the main carbon sources are glycerol and vegetable oil, with the latter usually in higher concentration. The purpose of this study is to investigate the effect of the ratio of the two carbon sources on process performance. Several carbon source ratios were tested, in the range between 0.4 to 8.8, and biomass productivity and pharmaceutical compound were analyzed as output. The consumption of these carbon sources was measured as well. The results show that a higher oil/glycerol ratio increases the production of the target molecule, suggesting a role of the stress caused by the unbalanced nutrient supply. The production of this molecule, indeed, is highly affected by environmental stress. This study therefore offers new ways to ensure this stress and new insights into the optimization of this essential fermentation process.