β-Lactamase inhibitors have emerged as an effective alternative to reduce the effects of resistance against β-lactam antibiotics. The Streptomyces genus is known for being an exceptional natural source of antimicrobials and β-lactamase inhibitors such as clavulanic acid, which is largely applied in clinical practice. To protect against the increasing prevalence of multidrug-resistant bacterial strains, new antibiotics and β-lactamase inhibitors need to be discovered and developed. This review will cover an update about the main β-lactamase inhibitors producers belonging to the Streptomyces genus; advanced methods, such as genetic and metabolic engineering, to enhance inhibitor production compared with wild-type strains; and fermentation and purification processes. Moreover, clinical practice and commercial issues are discussed. The commitment of companies and governments to develop innovative strategies and methods to improve the access to new, efficient, and potentially cost-effective microbial products to combat the antimicrobial resistance is also highlighted.

Microbial proteases, especially aspartic proteases, are an essential group of enzymes produced from different microorganisms. Microbial proteases have several applications, mainly in the food, beverage, cosmetic, and pharmaceutical industries, due to their efficiency in the processing and in the manufacturing stages. The yeast Rhodotorula mucilaginosa CBMAI 1528 was isolated from the Antarctic environment and was previously reported to have higher extracellular aspartic protease production. In addition, advances in the operational conditions of bioreactors for enzyme production are important to reduce the gap associated with scaling−up processes. This is the first study that evaluates the influence of oxygen transference (k_La) on the protease production of R. mucilaginosa yeast. To that end, batch cultures were created in a stirred tank bioreactor using Sabouraud dextrose broth at 25 °C for 72 h under k_La values from 18 to 135 h⁻¹. The results show that k_La (121 h⁻¹) obtained at 500 rpm and 1.5 vvm plays an important role in protease production (124.9 U/mL) and productivity (6.784 U/L.h) as well as biomass (10.4 g/L), μ_max (0.14 h⁻¹) and Y_x/s (0.484 g/g). In conclusion, R. mucilaginosa showed high yield production in aerobic culture with the efficiency of protease expression and secretion influenced by k_La. In this sense, our results could be used for further industrial investment.