Chemical diversity of scleractinian corals revealed by untargeted metabolomics and molecular networking

The chemical diversity of scleractinian corals is closely related to their physiological,ecological,and evolutionary status,and can be influenced by both genetic background and environmental variables.To investigate intraspecific variation in the metabolites of these corals,the metabolomes of four species(Pocillopora meandrina,Seriatopora hystrix,Acropora formosa,and Fungia fungites)from the South China Sea were analyzed using untargeted mass spectrometry-based metabolomics.The results showed that a variety of metabolites,including amino acids,peptides,lipids,and other small molecules,were differentially distributed among the four species,leading to their significant separation in principal component analysis and hierarchical clustering plots.The higher content of storage lipids in branching corals(P.meandrina,S.hystrix,and A.formosa)compared to the solitary coral(F.fungites)may be due to the high densities of zooxanthellae in their tissues.The high content of aromatic amino acids in P.meandrina may help the coral protect against ultraviolet damage and promote growth in shallow seawater,while nitrogen-rich compounds may enable S.hystrix to survive in various challenging environments.The metabolites enriched in F.fungites,including amino acids,dipeptides,phospholipids,and other small molecules,may be related to the composition of the coral's mucus and its life-history,such as its ability to move freely and live solitarily.Studying the chemical diversity of scleractinian corals not only provides insight into their environmental adaptation,but also holds potential for the chemotaxonomy of corals and the discovery of novel bioactive natural products.

Chemical diversity and biological function of indolediketopiperazines from marine-derived fungi

Natural products from marine-derived fungi have attracted considerable attention in the recent two decades.Indolediketopiperazines are one of the most important classes of marine natural products,mainly discovered from the fungal genera Penicillium,Aspergillus and Eurotium.These compounds span a wide range of chemical structures and bioactivities.This review summarizes 155 indolediketopiperazines that were discovered from marine-derived fungi from 2000 to early 2019 and primarily focuses on their chemical diversity and biological function.

Activation of microbial secondary metabolic pathways:Avenues and challenges

Microbial natural products are a tremendous source of new bioactive chemical entities for drug discovery.Next generation sequencing has revealed an unprecedented genomic potential for production of secondary metabolites by diverse micro-organisms found in the environment and in the microbiota.Genome mining has further led to the discovery of numerous uncharacterized‘cryptic’metabolic pathways in the classical producers of natural products such as Actinobacteria and fungi.These biosynthetic gene clusters may code for improved biologically active metabolites,but harnessing the full genetic potential has been hindered by the observation that many of the pathways are‘silent’under laboratory conditions.Here we provide an overview of the various biotechnological methodologies,which can be divided to pleiotropic,biosynthetic gene cluster specific,and targeted genome-wide approaches that have been developed for the awakening of microbial secondary metabolic pathways.

Co-culture:stimulate the metabolic potential and explore the molecular diversity of natural products from microorganisms

Microbial secondary metabolites have long been considered as potential sources of lead compounds for medicinal use due to their rich chemical diversity and extensive biological activities.However,many biosynthetic gene clusters remain silent under traditional laboratory culture conditions,resulting in repeated isolation of a large number of known compounds.The co-culture strategy simulates the complex ecological environment of microbial life by using an ecology-driven method to activate silent gene clusters of microorganisms and tap their metabolic potential to obtain novel bioactive secondary metabolites.In this review,representative studies from 2017 to 2020 on the discovery of novel bioactive natural products from co-cultured microorganisms are summarized.A series of natural products with diverse and novel structures have been discovered successfully by co-culture strategies,including fungus-fungus,fungus-bacterium,and bacterium-bacterium co-culture approaches.These novel compounds exhibited various bioactivities including extensive antimicrobial activities and potential cytotoxic activities,especially when it came to disparate marine-derived species and cross-species of marine strains and terrestrial strains.It could be concluded that co-culture can be an effective strategy to tap the metabolic potential of microorganisms,particularly for marine-derived species,thus providing diverse molecules for the discovery of lead compounds and drug candidates.

Marine-derived fungi as a source of bioactive indole alkaloids with diversifed structures

Marine-derived fungi are well known as rich sources of bioactive natural products.Growing evidences indicated that indole alkaloids,isolated from a variety of marine-derived fungi,have attracted considerable attention for their diverse,challenging structural complexity and promising bioactivities,and therefore,indole alkaloids have potential to be pharmaceutical lead compounds.Systemic compilation of the relevant literature.In this review,we demonstrated a comprehensive overview of 431 new indole alkaloids from 21 genera of marine-derived fungi with an emphasis on their structures and bioactivities,covering literatures published during 1982–2019.