Covering: up to February 2014 Microorganisms are well-known producers of a wide variety of bioactive compounds that are utilized not only for their primary metabolism but also for other purposes such as defense, detoxification, or communication with other micro- and macro-organisms. Natural products containing a ‘decalin ring’ occur often in microorganisms. They exhibit diverse and remarkable biological activities, including antifungal, antibacterial, anticancer and immunosuppressive activities, to name a few. This review surveys the natural decalin-type compounds that have been isolated from microorganisms, with emphasis on both chemical and biological implications. Total syntheses of some important decalin moiety-containing natural products are also highlighted.

Exploration of structurally novel natural products greatly facilitates the discovery of biologically active pharmacophores that are biologically validated starting points for the development of new drugs. Endophytes that colonize the internal tissues of plant species, have been proven to produce a large number of structurally diverse secondary metabolites. These molecules exhibit remarkable biological activities, including antimicrobial, anticancer, anti-inflammatory and antiviral properties, to name but a few. This review surveys the structurally diverse natural products with new carbon skeletons, unusual ring systems, or rare structural moieties that have been isolated from endophytes between 1996 and 2016. It covers their structures and bioactivities. Biosynthesis and/or total syntheses of some important compounds are also highlighted. Some novel secondary metabolites with marked biological activities might deserve more attention from chemists and biologists in further studies.

Artificial intelligence holds great promise for the design of antimicrobial peptides (AMPs); however, current models face limitations in generating AMPs with sufficient novelty and diversity, and they are rarely applied to the generation of antifungal peptides. Here, we develop an alternative pipeline grounded in a diffusion model and molecular dynamics for the de novo design of AMPs. The peptides generated by our pipeline have lower similarity and identity than those of other reported methodologies. Among the 40 peptides synthesized for an experimental validation, 25 exhibit either antibacterial or antifungal activity. AMP-29 shows selective antifungal activity against Candida glabrata and in vivo antifungal efficacy in a murine skin infection model. AMP-24 exhibits potent in vitro activity against Gram-negative bacteria and in vivo efficacy against both skin and lung Acinetobacter baumannii infection models. The proposed approach offers a pipeline for designing diverse AMPs to counteract the threat of antibiotic resistance.