Abstract
Dickeya zeae strain EC1 was recently shown to produce a new type of phytotoxins designated as zeamine and zeamine II, which are potent wide-spectrum antibiotics against Gram-positive and Gram-negative bacterial pathogens, suggesting their promising potential as clinical medicines. In this study, the optimized medium composition and culture conditions for biosynthesis of novel antibiotics zeamines have been established by using response surface methodology, largely increasing the yield of zeamines from original about 7.35 µg·mL−1 in minimal medium to about 150 µg·mL−1 in LS5 medium. The study identified the major factors contributing to zeamines production, which include nitrate, sucrose, asparaginate, mineral elements Mg2+ and K+, and optimized amount of phosphate. In addition, the results showed that overexpression of zmsK in D. zeae strain EC1 could further increase zeamines yield to about 180 µg·mL−1 in LS5 medium. The findings from this study could facilitate further characterization and utilization of these two novel antibiotics, and also provide useful clues for understanding the regulatory mechanisms that govern D. zeae virulence.
Highlights
Discovery of antibiotics is one of the landmark medical advances in human history, allowing treatment of infectious illnesses once commonly fatal
We showed recently that Dickeya zeae strain EC1, a plant bacterial pathogen that causes rice foot rot and maize stem rot diseases, produces a new type of antibiotics designated as zeamine and zeamine II [4, 5]
The results showed that sucrose was the best carbon source for zeamines production, followed by mannitol, glucose, glycerol and fructose, regardless whether NaNO3 or NH4NO3 was used as a nitrogen source (Fig. 2A, 2B; Table 3)
Summary
Discovery of antibiotics is one of the landmark medical advances in human history, allowing treatment of infectious illnesses once commonly fatal. We showed recently that Dickeya zeae strain EC1, a plant bacterial pathogen that causes rice foot rot and maize stem rot diseases, produces a new type of antibiotics designated as zeamine and zeamine II [4, 5]. Zeamine II is a long chain aminated polyketide and zeamine shares the same polyketide structure as zeamine II with an extra valine derivative moiety conjugated to the primary amino group of zeamine II. These antibiotics showed potent microbicidal activities against a wide range of Gram-positive and Gram-negative bacterial pathogens including multidrug-resistant bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa [4], but the mechanism of inhibitory action remains unknown. A gene cluster encoding the biosynthesis of zeamine antibiotics has recently been characterized in Serratia plymuthica [7]
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