Marine bacterial metabolites in anticancer drug discovery: Ecological insights, mechanisms of action, and clinical translation

Marine ecosystems contain a pool of diversely chemical microorganisms with the ability of producing structurally unique bioactive metabolites. Bacteria derived in the sea have become a major source of innovative
anticancer agents with particular activity and lower toxicity of the system. Recent findings have depicted the
remarkable anticancer effects of marine bacterial metabolites, including Seriniquinone, Salinosporamide A,
Didemnin B and Bryostatin analogues, which have a high level of cytotoxic, pro-apoptotic, and immunomodulatory effects on a wide range of aggressive and treatment-resistant cancers. Marine-based molecules are less
likely to damage normal tissues as compared to conventional chemotherapeutic agents, have a high likelihood of
attacking particular signalling pathways, mitochondria, proteasomes and redox homeostasis. This review explains the application of marine bacteria in anticancer drug discovery and highlights ecological features of
marine bacteria, structural and functional variation of their secondary metabolites, and molecular pathways of
their anticancer effects. These pathways are cell cycle arrest, regulation of intrinsic apoptotic pathway, autophagy, proteasome, and immune. The review also assesses the preclinical data and new translational data on the
relevance of marine bacterial compounds in cancer treatment. It is also concerned with the issue of large-scale
manufacturing, the complexity of biosynthesis, and clinical translation. As the field of marine microbiology,
chemical biology, and cancer pharmacology evolves, additional studies of marine bacterial biodiversity, genomics, metabolomics, and synthetic biology are highly likely to result in the next generation of anticancer agents,
resistance circumvention, and patient outcomes.