Most natural chemical compounds produced by living organisms are built from a familiar set of elements: carbon, hydrogen, nitrogen and oxygen. A small group of compounds breaks that pattern, and researchers say those outliers could hold significant potential for medicine and biotechnology.
A new review study published in Natural Product Reports examines decades of discoveries involving metabolites that contain atypical elements, including boron, iodine, fluorine, selenium and arsenic. The review covers findings reported between 1944 and 2025 and was led by Professor Seoung Rak Lee, an assistant professor at the College of Pharmacy at Pusan National University, as reported by Phys.org.
These unusual compounds are produced by microbes, plants and marine organisms. Their chemical structures are rare, but researchers say that rarity comes with advantages. Incorporating an atypical atom into a compound can alter how easily it crosses cell membranes, improve how long it survives in the body, promote chemical reactions involving electrons, and enhance its overall biological activity.
Each element enters these compounds through its own specialized pathway. Fluorine is introduced through rare biological carbon-fluorine bond formation. Selenium is incorporated through dedicated selenium-carbon bond-forming pathways. Arsenic-containing compounds often arise through S-adenosyl-L-methionine dependent methylation and subsequent transformations. Boron is typically introduced through nonenzymatic boronate or borate complexation, while iodine is incorporated through halogenase- or haloperoxidase-mediated reactions.
The biological activities tied to these compounds are wide-ranging. Boron-containing natural products, including boromycin and tartrolons, exhibit antibacterial, antiparasitic, antiviral, immunomodulatory and quorum-sensing activities. Fluorinated natural products such as fluoroacetate, 4-fluoro-L-threonine and nucleocidin include potent toxins and antimicrobial compounds. Arsenic-containing metabolites span a broad spectrum, with some compounds serving as relatively inert storage or detoxification forms.
Lee explained the motivation behind pulling together this body of research. "While these compounds are scarce, they reveal how organisms overcome major challenges to synthesize these metabolites that are difficult to achieve under normal biological conditions. We wanted to discuss the enzymatic foundations of these distinctive transformations," he said.
The review is intended to give researchers a clearer picture of where these unusual compounds come from and what makes them biologically active, which could help guide future efforts to develop new drugs or agricultural treatments based on their properties.
