Abstract
Penicillium sp. WC-29-5 was co-cultured with Streptomyces fradiae 007 to produce five natural products (1–3, 4a and 4b) that were isolated and characterized by spectroscopic analysis. Interestingly, these compounds were found to be different from those produced in discrete fungal and bacterial controls. Among these compounds, the absolute configurations of compounds 4a and 4b were determined for the first time by X-ray single crystal diffraction experiments and electronic circular dichroism (ECD) calculations. An evaluation of the cytotoxic activities of these compounds revealed that 4b was moderately cytotoxic towards HL-60 and H1975 tumor cells with IC50 values of 3.73 and 5.73 µM, respectively, whereas compound 4a was only moderately cytotoxic towards H1975 cells with an IC50 value of 3.97 µM.
Highlights
Natural products have proven to be an incredible resource for drug discovery [1] and the microorganisms responsible for the production of natural products can be considered in some respects as a type of renewable and eco-friendly resource
Many of the microbial gene clusters involved in the synthesis of natural products, are silent under traditional lab conditions [2,3,4], and significant research efforts have been devoted to developing new strategies and approaches for activating silent gene clusters to increase the diversity and availability of microbial natural products
WC-29-5 and S. fradiae 007 were co-cultivated in the same medium in the current study to induce the production of different bioactive compounds as a consequence of the competitive nature of the environment
Summary
Natural products have proven to be an incredible resource for drug discovery [1] and the microorganisms responsible for the production of natural products can be considered in some respects as a type of renewable and eco-friendly resource. From the perspective of cooperative interactions, the co-cultivation or mixed fermentation of two or more microbes represents a promising approach for simulating physiological conditions and activating silent gene clusters [3,5,6,7]. As part of our ongoing research towards identifying new bioactive natural products from marine-derived microorganisms [8,9,10], we recently became interested in evaluating the mixed fermentation of two microbes and found that the co-cultivation of Penicillium sp. WC-29-5 and Streptomyces fradiae 007 led to the production different metabolites to those produced by each species in isolation (Figure 1). We report the isolation, structural elucidation and evaluation of the cytotoxicity of the metabolites produced by the co-cultivation of Penicillium sp. WC-29-5 and co-cultivation of two strains from up to down (HPLC eluent: 0–30 min, 50% MeOH; flow rate: 1 mL/min; detection wavelength: 202 nm)
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