The effects of nitrogen sources on streptolydigin production and distribution of secondary metabolites were investigated for flask cultured S.lydicus AS 4.2501.When peptone,asparamide,and glutamic acid were ex- amined as the nitrogen source,respectively,liquid chromatography-mass spectrometry(LC-MS)and photodiode array(PDA)analyses revealed the formation of two analogues of streptolydigin in the fermentation broth.When soybean meal was used as the source of nitrogen,three analogues of streptolydigin were detected.The use of am- monium sulfate as a source of nitrogen resulted in a lower pH value of the fermentation system,thus inhibiting streptolydigin biosynthesis and changing the metabolic profiling.Among the nitrogen sources that were made use of,glutamic acid was most favorable to the formation of streptolydigin.Simultaneously,this study also showed that the changing nitrogen sources resulted in altering the production and relative ratios of streptolydigin and its analogues.
To achieve higher antibiotic streptolydigin productivity through metabolic regulation, propionate was fed during the fermentation of Streptomyces lydicus AS 4.2501. The effects of propionate feeding on streptolydigin production and intracellular fluxes were investigated. The highest streptolydigin production yield of 95.10mg·L-1 was obtained when 2mmol·L-1 of sodium propionate was added at 60h of cultivation into shake-flask culture. This yield is 23.06% higher when compared to that of a batch culture without propionate supplementation. It was also found that when propionate was added, much more organic acids were excreted. Metabolic flux analysis was per-formed and it demonstrated that the carbon fluxes of the pentose phosphate pathway and the anaplerotic reaction were significantly increased after propionate feeding. The carbon flux from pyruvate to acetyl-CoA was determined to be 24.7, which was 12.27% higher than that in the batch culture. This study indicated that the glu-cose-6-phosphate and pyruvate nodes were potential bottlenecks for increasing streptolydigin productivity. Potential targets and strategies that could be manipulated through genetic and process engineering to increase the production of streptolydigin were also suggested.
