The dynamic regulation of nitrogen and phosphorus in the early phase of fermentation improves the erythromycin production by recombinant Saccharopolyspora erythraea strain

Qiang Zhang,Si-Liang Zhang,Ying-Ping Zhuang,Yong Chen,Yang Gao,Ming Hong,Ju Chu

doi:10.1186/s40643-014-0015-7

Abstract

Abstract Background Erythromycin production often has concern with the consumption rate of amino nitrogen and phosphate, especially in the early fermentation phase. The dynamic regulation of nitrogen and phosphorus was put forward based on the comprehensive analysis of the contents of phosphorus and nitrogen in different nitrogen sources as well as the relations between nitrogen consumption and phosphorus consumption. Results Firstly, the unstable nitrogen source, corn steep liquor, was substituted with the stable nitrogen source, yeast powder, with little effects on erythromycin production. Secondly, feeding phosphate in the early fermentation stage accelerated the consumption of amino nitrogen and ultimately increased erythromycin production by approximately 24% as compared with the control (without feeding potassium dihydrogen phosphate). Thirdly, feeding phosphate strategy successfully applied to 500 L fermenter with the final erythromycin concentration of 11839 U/mL, which was 17.3% higher than that of the control. Finally, the application of condensed soy protein (a cheap nitrogen source with low phosphorus content) combined with phosphate feed strategy led to a 13.0% increase of the erythromycin production as compared with the control (condensed soy protein, without feeding potassium dihydrogen phosphate). Conclusions Appropriately feeding phosphate combined with rational nitrogen regulation in the early fermentation phase was an effective way to improve erythromycin production.

Highlights

Erythromycin production often has concern with the consumption rate of amino nitrogen and phosphate, especially in the early fermentation phase
The erythromycin fermentation with yeast powder as the metabolized nitrogen source Owing to the instability of corn steep liquor, the substitution of corn steep liquor with yeast powder was investigated
The results showed that the erythromycin production of yeast powder medium was reached to 9,746 U/mL at 192 h, which was similar to that with corn steep liquor medium

Summary

Introduction

Erythromycin production often has concern with the consumption rate of amino nitrogen and phosphate, especially in the early fermentation phase. Erythromycin is a kind of polyketide antibiotic produced by Saccharopolyspora erythraea through industrial fermentation. Erythromycin has received much attention because its semi-synthetically modified derivatives, such as azithromycin, roxithromycin, and clarithromycin, are widely used in the treatment of infectious diseases [1,2]. It has been reported that the genetic engineering technology, used to replace corn steep liquor, so that the erythromycin production could be maintained at a stable level. Our data showed that the erythromycin production was little affected by the substitution of corn steep liquor with yeast powder. It was found that phosphorus content limited the consumption rate of amino nitrogen

Methods

Results

Conclusion