Study of Steffimycin Biosynthetic Gene Cluster Distribution among Marine Actinomycetes and its Molecular Interaction to CDK1 for Anticancer Research

Cancer is one of the leading health problems worldwide contributing to mortality along with COVID19 and heart disease. Several studies indicated that Cyclin-Dependent Kinase 1 (CDK1) served as a potential prognostic biomarker and target for several cancer types, e.g., lung and breast cancer. Marine actinobacteria are recognized as important producers of bioactive compounds, especially genus Streptomyces. One of the Streptomyces-derived secondary metabolites, steffimycin is classified as an anthracycline drug. Therefore, this study aimed to investigate the distribution of steffimycin biosynthetic gene cluster (BGC) among marine actinobacteria based on computational analysis. Total of 491 BGCs were predicted from 32 marine actinobacterial complete genomes by AntiSMASH. Steffimycin BGCs from marine Streptomyces were classified into terpene types by BiG-SCAPE. The construction of phylogenomic relationship using the stfK, steffimycin core gene as query by CORASON showed that steffimycin-related BGCs were distributed among marine Streptomyces. Steffimycin clade was identified as the candidate for putative steffimycin producer. Moreover, the simulation of the compatibility between steffimycin D with CDK1 by RosettaLigand docking revealed the possible interaction with top interface score at -9.909 kcal/mol which was lower than that of the positive control (dinaciclib). The steffimycin T35, I59, Q235 and D236 amino acid residues interacted with helix in the CDK1 protein. This docking results suggested the binding between steffimycin D and CDK1 as an anticancer target. In the future, in silico, genome mining analysis coupled with CDK1 molecular docking could accelerate screening of anticancer compound in actinobacteria and other biological sources.