Biosynthetic potential and anti-tumor natural product η-rhodomycinone of the endophyte Streptomyces sp. SZC001 in Sinomenium acutum

Abstract:

[Objective] To investigate the biosynthetic potential of the endophyte Streptomyces sp. SZC001 in Sinomenium acutum and explore the unknown active natural products. [Methods] SZC001 was isolated by surface sterilizing method and its full-length genome sequence was obtained by third-generation and second-generation sequencing. Then, the biosynthetic potential of SZC001 was evaluated by antiSMASH analysis. Fermentation was carried out with four media, and the compounds were separated and identified by silica gel column chromatography, high-performance liquid chromatography, high-resolution mass spectrometry and nuclear magnetic resonance. The CCK-8 assay was employed to examine the cytotoxicity of the target compounds. [Results] The strain was identified as Streptomyces sp. SZC001, with a genome length of 9 109 166 bp and the G+C content of 71.08%. The antiSMASH analysis showed that the genome of the strain contained a total of 31 biosynthetic gene clusters (BGCs), among which 17 BGCs had less than 40% similarity with the known BGCs. The strain produced several anthracyclines in four media, and the two most abundant compounds 1 and 2 were isolated and identified. Compound 1 is the known compound ε-rhodomycinone and compound 2 is a new compound η-rhodomycinoe, which is derived from α₂-rhodomycinone by derivatization of the hydroxyl group at the C-10 position and transfer of the hydroxyl group at the 6-position to the 11-position of the backbone. Both compounds 1 and 2 showed relatively strong inhibitory effects on two tumor cell lines, with IC₅₀ of 1.55–4.59 μmol/L. [Conclusion] SZC001 is a strain that holds the potential for the exploration of active natural products. The anthracyclines produced by the strain exhibit anti-tumor activities and warrant further development and utilization. This study enriches ε-rhodomycinone derivatives, furnishing a foundation for the subsequent exploitation of the endophytic resources of S. acutum.