Abstract

Since first isolated from the lipophilic extract of Streptomyces sp. SF2583, streptochlorin, has attracted a lot of attention because of its various pharmacological properties, such as antibiotic, antiallergic, antitumor, and anti-inflammatory activities. For the efficient preparation of streptochlorin from a producing strain Streptomyces sp. SYYLWHS-1-4, we developed a combinative method by using response surface methodology (RSM) and high-speed counter-current chromatography (HSCCC). In the fermentation process, we used RSM to optimize the condition for the efficient accumulation of streptochlorin, and the optimal parameters were: yeast extract 1.889 g/L, soluble starch 8.636 g/L, K2HPO4 0.359 g/L, CaCl2 2.5 g/L, MgSO4 0.625 g/L, marine salt 25 g/L, medium volume 50%, initial pH value 7.0, temperature 27.5 °C, which enhanced streptochlorin yield by 17.7-fold. During the purification process, the preparative HSCCC separation was performed using a petroleum ether–ethyl acetate–methanol–water (9:0.8:5:5, v/v/v/v) biphasic solvent system, where 300 mg of crude sample yielded 16.5 mg streptochlorin with over 95% purity as determined by UPLC. Consequently, the combination method provided a feasible strategy for highly effective preparation of streptochlorin, which ensured the supply of large amounts of streptochlorin for in vivo pharmacological assessments or other requirements.

Highlights

  • Microbial natural products represent an important source of novel therapeutic agents [1,2].Streptochlorin (Figure 1), originally isolated from Streptomyces strain SF2583 [3], is an indole alkaloid with a variety of significant biological activities, such as antibiotic [4,5], anti-inflammatory [6], antiallergic [7] and antitumor [7,8,9] effects

  • A total of 20 tests were conducted in triplicate to select the significant variables for streptochlorin production

  • Plackett-Burman design (PBD) results indicated that yeast extract, soluble starch and K2 HPO4 exhibited a negative effect on streptochlorin production

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Summary

Introduction

Streptochlorin (Figure 1), originally isolated from Streptomyces strain SF2583 [3], is an indole alkaloid with a variety of significant biological activities, such as antibiotic [4,5], anti-inflammatory [6], antiallergic [7] and antitumor [7,8,9] effects. A marine Streptomyces strain SYYLWHS-1-4, which was cultivated from a mangrove sediment sample by microbial trap [10], was found to produce streptochlorin. Under standard fermentation conditions, the yield of streptochlorin in the spent medium is relatively low, and its isolation and preparation requires complex chromatographic. 21, 693 steps, often leadingMolecules to 2016, serious losses. Optimization of fermentation conditions for streptochlorin production and developing an efficient preparation method are extremely urgent

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