Optimization of nutrients for dinactin production by a marine Streptomyces sp. from the high latitude Arctic

Streptomyces sp. R-527F, which produces the macrotetrolide antibiotic dinactin, was isolated from the sediments of the Arctic Ocean. In this work, optimization of the nutrients required for dinactin production including medium development and precursor stimulation, were investigated. Optimization of the medium and replacement of polar sea water were achieved using a one factor at a time experiment in conjunction with statistical analysis using methods covering Plackett–Burman design, the steepest descent method and central composite design. Dinactin production in the optimized medium was 160.8 mg/L, which was 47 fold higher than the control. Supplementation of the fermentation with exogenous acetate (1.5 mmol/L), succinate (6 mmol/L), malonate (24 mmol/L) and citrate (6 mmol/L) further enhanced dinactin biosynthesis by 42.7, 122.3, 66.7, and 62.1%, respectively. The precursors, in particular succinate, facilitated sugar use and also increased pH levels. Furthermore, a six-pulse feeding of total 6 mmol/L succinate in a 5 L bioreactor fermentation yielded a maximal production of 279.0 mg/L dinactin, 124.1% higher than that without precursor stimulation. This nutritional regulation process is easy to scale up and holds the potential for adaptation to industrial use.