Natural products built from carbon, hydrogen, nitrogen, and oxygen dominate biology’s chemical palette—but a growing body of work shows nature can also deploy rarer “guest” elements. A new literature review in Natural Product Reports highlights metabolites containing atypical atoms, including boron, fluorine, iodine, selenium, arsenic, and the transition metals vanadium and molybdenum, mapping how organisms turn these elements into functional chemistry.
The review compiles discoveries reported from 1944 to 2025, focusing on both structure and mechanism. Despite their scarcity, these compounds illuminate how living systems overcome synthetic challenges that conventional biochemical logic struggles to solve, particularly when forming difficult element–carbon or element–heteroatom bonds.
A central theme is that elemental substitution can reshape molecular behavior. Incorporating atypical atoms may tune lipophilicity, enhance metabolic stability, introduce redox activity, enable metal coordination, and alter biological potency. In other words, the unusual atomic composition often supplies properties that standard primary-element scaffolds cannot easily replicate.
The mechanisms for installing these elements are diverse and sometimes counterintuitive. Fluorine, for example, is frequently linked to rare pathways that build carbon–fluorine bonds. Selenium appears through dedicated selenium–carbon forming strategies, while arsenic-containing metabolites often reflect SAM-dependent methylation followed by downstream transformations.
Boron is treated differently: many boron metabolites arise through boronate or borate complexation rather than straightforward enzymatic insertion. Iodine, meanwhile, is frequently introduced via halogenase- or haloperoxidase-mediated reactions, underscoring how enzyme families can be repurposed to manage reactive halogens.
Across metabolite families, the biological outcomes span the spectrum of survival chemistry. Boron-bearing compounds include examples with antibacterial, antiparasitic, antiviral, immunomodulatory, and quorum-sensing activities. Fluorinated metabolites demonstrate how carbon–fluorine chemistry can generate potent toxins and antimicrobials.
Arsenic compounds range from relatively inert storage and detoxification forms in marine systems to higher-activity lipids and toxic derivatives. Selenium-containing metabolites often support antioxidant defense and redox regulation, while iodinated molecules contribute to antimicrobial and cytotoxic protection.
Finally, vanadium and molybdenum are framed largely as biological cofactors that assist core life processes such as nitrogen fixation, halogenation, nitrate reduction, sulfite detoxification, and purine metabolism. Overall, these metabolites connect element handling to detoxification, signaling, ion transport, and large-scale biogeochemical cycling.
“Our findings provide a valuable framework for discovering new bioactive natural products and biosynthetic enzymes with applications in drug discovery, biocatalysis, and synthetic biology,” concludes the study’s lead author, emphasizing that understanding atypical atom incorporation could inspire new fluorination and selenation approaches for sustainable biotechnology and therapeutics.
Subject of Research: Not specified beyond “natural products with atypical atoms” (review article)
Article Title: Natural products with atypical atoms: unveiling structures, biosynthetic pathways, and bioactivities
News Publication Date: 4-Jun-2026
Web References: https://doi.org/10.1039/d5np00083a
References: 10.1039/d5np00083a
Image Credits: Pusan National University
Keywords: natural products, atypical atoms, boron, fluorine, iodine, selenium, arsenic, biosynthesis, enzyme mechanisms, drug discovery
