“…Although SF is a well-established technology applied in large-scale industrial enzyme production due to better monitoring and ease of handling, it has several disadvantages, such as the generation of large amounts of wastewater, difficulties in effluent treatment processes, and a high production cost [ 78 , 79 ]. The performance of SF can be influenced by various factors such as the carbon and nitrogen sources, temperature, pH, fermentation time, agitation, and inoculum size [ 80 , 81 ]. Soliman et al (2020) studied the impact of sixteen different independent factors, including carbon sources, energy sources, metals, nitrogen sources, agitation speed, temperature, inoculum size, incubation time, and pH, on the production of L-asparaginase by Streptomyces fradiae NEAE-82 by applying a Plackett–Burman statistical design, and found that L-asparagine was the most significant positive independent factor ( p -value 0.0092) affecting L-asparaginase production [ 55 ].…”