Genome sequencing has revealed that microorganisms have the potential to produce many more natural products than previously thought; the challenge is to establish efficient ways to “wake up” those “sleeping” biosynthetic pathways or genes, which are undoubtedly expressed in nature under specific conditions that are not normally reproduced in the laboratory. To activate these cryptic natural products, co-cultivation of cross-kingdom microorganisms between Candida albicans and Streptomyces longshengensis was performed in this study. A novel peak generated through co-culture was isolated and analyzed by a high-performance liquid chromatograph (HPLC), and its chemical structure was further determined by using mass spectrum (MS) and nuclear magnetic resonance (NMR) analyses. Bioassays of antimicrobial and antitumor activities were performed, and heterologous expression in Escherichia coli was attempted. The chemical structure was identified as tryptophol, and the bioassays revealed that tryptophol showed antitumor activity with IC50 values of 154.5, 144.3, 122.6, and 110.7 μg/mL against A549, MC38, HepG2, and MCF-7 cells, respectively. As a valuable compound, tryptophol was also heterologously expressed in E. coli C41 to address the drawbacks of chemical synthesis. These findings combine co-cultivation with genetic engineering for tryptophol biosynthesis, expanding its antitumor application and laying a foundation for its industrial and sustainable production.
Li et al. (Wed,) studied this question.