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All life on Earth is unified by its use of a shared set of component chemical compounds and reactions, providing a detailed model for universal biochemistry. However, this notion of universality is specific to known biochemistry and does not allow quantitative predictions about examples not yet observed. Here, we introduce a more generalizable concept of biochemical universality that is more akin to the kind of universality found in physics. Using annotated genomic datasets including an ensemble of 11,955 metagenomes, 1,282 archaea, 11,759 bacteria, and 200 eukaryotic taxa, we show how enzyme functions form universality classes with common scaling behavior in their relative abundances across the datasets. We verify that these scaling laws are not explained by the presence of compounds, reactions, and enzyme functions shared across known examples of life. We demonstrate how these scaling laws can be used as a tool for inferring properties of ancient life by comparing their predictions with a consensus model for the last universal common ancestor (LUCA). We also illustrate how network analyses shed light on the functional principles underlying the observed scaling behaviors. Together, our results establish the existence of a new kind of biochemical universality, independent of the details of life on Earth’s component chemistry, with implications for guiding our search for missing biochemical diversity on Earth or for biochemistries that might deviate from the exact chemical makeup of life as we know it, such as at the origins of life, in alien environments, or in the design of synthetic life.

The Solar System is becoming increasingly accessible to exploration by robotic missions to search for life. However, astrobiologists currently lack well-defined frameworks to quantitatively assess the chemical space accessible to life in these alien environments. Such frameworks will be critical for developing concrete predictions needed for future mission planning, both to determine the potential viability of life on other worlds and to anticipate the molecular biosignatures that life could produce. Here, we describe how uniting existing methods provides a framework to study the accessibility of biochemical space across diverse planetary environments. Our approach combines observational data from planetary missions with genomic data catalogued from across Earth and analyzed using computational methods from network theory. To demonstrate this, we use 307 biochemical networks generated from genomic data collected across Earth and “seed” these networks with molecules confirmed to be present on Saturn's moon Enceladus. By expanding through known biochemical reaction space starting from these seed compounds, we are able to determine which products of Earth's biochemistry are, in principle, reachable from compounds available in the environment on Enceladus, and how this varies across different examples of life from Earth (organisms, ecosystems, planetary-scale biochemistry). While we find that none of the 307 prokaryotes analyzed meet the threshold for viability, the reaction space covered by this process can provide a map of possible targets for detection of Earth-like life on Enceladus, as well as targets for synthetic biology approaches to seed life on Enceladus. In cases where biochemistry is not viable because key compounds are missing, we identify the environmental precursors required to make it viable, thus providing a set of compounds to prioritize for detection in future planetary exploration missions aimed at assessing the ability of Enceladus to sustain Earth-like life or directed panspermia.

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