Optimization of fermentation conditions and medium compositions for the production of chrysomycin a by a marine-derived strain Streptomyces sp. 891.

Chrysomycin A is one of the valuable drug leads used to treat infectious diseases such as tuberculosis and methicillin-resistant Staphylococcus aureus. In order to increase its yield, this work firstly focuses on optimization of fermentation conditions and medium compositions of a wild-type chrysomycin A-producing strain Streptomyces sp. 891 from marine sediment. By single-factor experiment, effects of fermentation conditions (fermentation time, seed age, initial pH, inoculum amount, liquid loading, shaking speed) and medium composition (carbon sources, nitrogen sources, inorganic salts) on the yield of chrysomycin A were carefully evaluated and analyzed followed by optimization at shake-flask level. The results indicated its optimal fermentation conditions for producing chrysomycin A were as follows: fermentation time 168 h, seed age 48 h, initial pH 6.5, inoculum amount 5.0%, liquid loading 30 mL in 250-mL Erlenmeyer flask and shaking speed 220 rpm. By orthogonal test, the optimal fermentation medium constitutes 40 g/L glucose, 20 g/L corn starch, 25 g/L hot-pressed soybean flour, 3 g/L CaCO3. Verification tests suggested the yield of chrysomycin A under optimized conditions reaches up to 3648 ± 119 mg/L, which is increased by almost 5 times. These findings definitely pave the way for scale-up preparation of chrysomycin A and application in the pharmaceutical industry.

Metabolic engineering of Corynebacterium glutamicum S9114 to enhance the production of l-ornithine driven by glucose and xylose.

l-ornithine, an important amino acid, is widely used in food and medicine industries. l-ornithine production mainly relies on microbial fermentation, which may not meet the industrial requirement owing to the poor fermentation ability of available strains. Herein, mscCG2 deletion, CgS9114_12202 (gdh2) overexpression and rational modulation in tricarboxylic acid cycle was firstly demonstrated to increase l-ornithine production in engineered Corynebacterium glutamicum S9114. By further modulate glucose utility result in strain SO26 that produced 38.5 g/L or 43.6 g/L of l-ornithine in shake flask and fed-batch fermentation, respectively. This was 25% higher than that of the original strain (30.8 g/L) and exhibits highest titer reported in shake-flask. Moreover, the incorporation of xylose pathway in the engineered strain resulted in the highest l-ornithine production titer (18.9 g/L) and yield (0.40 g/g xylose) with xylose substrate. These results illustrate the tremendous potential of the engineered strain C. glutamicum S9114 in l-ornithine production.