Polyene macrolactams are a special group of natural products with great diversity, unique structural features, and a wide range of biological activities. Herein, a cryptic gene cluster for the biosynthesis of putative macrolactams was disclosed from a sponge-associated bacterium, Streptomyces sp. DSS69, by genome mining. Cloning and heterologous expression of the whole biosynthetic gene cluster led to the discovery of weddellamycin, a polyene macrolactam bearing a 23/5/6 ring skeleton. A negative regulator, WdlO, and two positive regulators, WdlA and WdlB, involved in the regulation of weddellamycin production were unraveled. The fermentation titer of weddellamycin was significantly improved by overexpression of wdlA and wdlB and deletion of wdlO. Notably, weddellamycin showed remarkable antibacterial activity against various Gram-positive bacteria including MRSA, with MIC values of 0.10-0.83 μg/mL, and antifungal activity against Candida albicans, with an MIC value of 3.33 μg/mL. Weddellamycin also displayed cytotoxicity against several cancer cell lines, with IC50 values ranging from 2.07 to 11.50 µM.

OBJECTIVE: Microbial production of biopolymers is typically associated with high viscosity and suitable mixing plays an important role in their production. Due to the nature of Streptococcus strains in high production of lactic acid and consequently high consumption of NaOH, which is associated with increased viscosity and reduced mixing caused by hyaluronic acid production, the injected NaOH accumulates and causes cells loss, and decreases in quantity and quality of the produced hyaluronic acid.
RESULTS: In this study, the effect of increasing dilution of media culture of Streptococcus zooepidemicus fed-batch culture during pH control by NaOH on mixing time, volumetric oxygen transfer coefficient, and increasing hyaluronic acid production in a 2-L fermenter were studied. The results showed that significant increasing dilution causes reduction mixing time, remarkable improvement volumetric oxygen transfer coefficient, hyaluronic acid production enhancement from 6.6 to 8.4 g/L, and diminution the consumption of NaOH.
CONCLUSIONS: Dilution of media culture of S. zooepidemicus fed-batch culture by the pH controlling agent achieved one of the highest amounts of hyaluronic acid that was reported recently. This method does not require any automatic control and can be used at a low cost to produce other soluble extracellular biopolymers.