Enhanced Natamycin production by Streptomyces natalensis in shake-flasks and stirred tank bioreactor under batch and fed-batch conditions

Abstract

Background Natamycin is an antifungal polyene macrolide antibiotic with wide applications in health and food industries. Currently, it is the only antifungal food additive with the GRAS status (Generally Regarded as Safe). Results Natamycin production was investigated under the effect of different initial glucose concentrations. Maximal antibiotic production (1.58 ± 0.032 g/L) was achieved at 20 g/L glucose. Under glucose limitation, natamycin production was retarded and the produced antibiotic was degraded. Higher glucose concentrations resulted in carbon catabolite repression. Secondly, intermittent feeding of glucose improved natamycin production due to overcoming glucose catabolite regulation, and moreover it was superior to glucose-beef mixture feeding, which overcomes catabolite regulation, but increased cell growth on the expense of natamycin production. Finally, the process was optimized in 7.5 L stirred tank bioreactor under batch and fed-batch conditions. Continuous glucose feeding for 30 h increased volumetric natamycin production by about 1.6- and 1.72-folds in than the batch cultivation in bioreactor and shake-flasks, respectively. Conclusions Glucose is a crucial substrate that significantly affects the production of natamycin, and its slow feeding is recommended to alleviate the effects of carbon catabolite regulation as well as to prevent product degradation under carbon source limitation. Cultivation in bioreactor under glucose feeding increased maximal volumetric enzyme production by about 72% from the initial starting conditions.

Characterization of the Metabolic Response of Streptomyces clavuligerus to Shear Stress in Stirred Tanks and Single-Use 2D Rocking Motion Bioreactors for Clavulanic Acid Production

“…An increase of the agitation rate in the range from 200 to 600 rpm was observed to favor the production of neomycin in STR cultivations of S. fradiae, but a negative effect was reported for agitation values above 600 rpm [43]. Similarly, natamycin production by S. natalensis increased up to 7-fold when the agitation was increased from 50 to 250 rpm in an STR [44,45]. In shake-flask cultures of S. pristinaespiralis, an increase in power dissipation between 2 and 5 kW m −3 increased pristinamycin accumulation [46].…”

Multi-Omics Approach in Amelioration of Food Products

“…Natamycin extracted from Streptomyces gilvosporeus is or Streptomyces natalensis are used in the food industry to solve this problem. It asserts to have antimicrobial impacts against molds and yeasts by increasing the shelf life of cheese, meat, beverages, and new dairy items ( Elsayed et al, 2019 ). In addition, bacteriocins 7293A and 7293B from LAB and Weisselahellenica BCC 7239 were active antibodies to prevent Aeromonashydrophila, E. coli, P. aeruginosa , and S. typhimurium in meat and meat products ( Costa et al, 2019 ).…”

Application of bacteriocins in food preservation and infectious disease treatment for humans and livestock: a review

“…To solve this problem, natamycin extracted from Streptomyces natalensis or Streptomyces gilvosporeus is claimed to have antimicrobial effects against yeasts and molds, which can prolong the storage period of cheese, fresh dairy products, processed meat and beverages. 84 In addition, mycocin is a bacteriocin produced by Debaryomyces hansenii DSMZ70238 that can be used in the preservation of meat and meat products by inhibiting the growth of L. monocytogenes. 85 Furthermore, bacteriocins 7293A and 7293B, which are produced by lactic acid bacteria, Weissella hellenica BCC 7239 was proved to be an effective antimicrobial agent for the inhibition of P. aeruginosa, Aeromonas hydrophila, S. typhimurium and E. coli in meat and meat products.…”