Natural products from mangrove sediments-derived microbes: Structural diversity, bioactivities, biosynthesis, and total synthesis

The mangrove forests are a complex ecosystem, and the microbial communities in mangrove sediments play a critical role in the biogeochemical cycles of mangrove ecosystems. Mangrove sediments-derived microbes (MSM), as a rich reservoir of natural product diversity, could be utilized in the exploration of new antibiotics or drugs. To understand the structural diversity and bioactivities of the metabolites of MSM, this review for the first time provides a comprehensive overview of 519 natural products isolated from MSM with their bioactivities, up to 2021. Most of the structural types of these compounds are alkaloids, lactones, xanthones, quinones, terpenoids, and steroids. Among them, 210 compounds are obtained from bacteria, most of which are from Streptomyces, while 309 compounds are from fungus, especially genus Aspergillus and Penicillium. The pharmacological mechanisms of some representative lead compounds are well studied, revealing that they have important medicinal potentials, such as piericidins with anti-renal cell cancer effects, azalomycins with anti-MRSA activities, and ophiobolins as antineoplastic agents. The biosynthetic pathways of representative natural products from MSM have also been summarized, especially ikarugamycin, piericidins, divergolides, and azalomycins. In addition, the total synthetic strategies of representative secondary metabolites from MSM are also reviewed, such as piericidin A and borrelidin. This review provides an important reference for the research status of natural products isolated from MSM and the lead compounds worthy of further development, and reveals that MSM have important medicinal values and are worthy of further development.