Metals are an essential part of life comprising cofactors, nutrients, chlorophyll, electron acceptors and donors, color creators and more. Although man has used metals extensively since copper was discovered in 9000 B.C.E., we are just beginning to appreciate the ability of biology to manipulate metals [1] . Uranium is not considered an essential metal for biological processes, but has become an essential part of lifestyle in the 20^th century through the development of nuclear technologies from weapons to clean energy to medicine. Uranium is the largest stable element found on the planet Earth. While radioactive, the half-life is 4.5 billion years, meaning that it decays very slowly. Uranium is found naturally throughout the Earth’s crust with an average of 2.7 mg of uranium per kg of crust. Although uranium concentrations are much higher in naturally-occurring uranium deposits, some of which are mined for uranium [2] [3] , in the Earth’s crust, uranium is found mostly in mineral complexes [4] .

Despite the low-level natural abundance of uranium in soils, human activities have introduced dramatically high concentrations of uranium to water and soils near uranium mines, near other metal mines that also have high uranium content, near nuclear weapons manufacturing and testing sites, and near nuclear power plants―creating high concentrations of uranium in formerly pristine sites [5] . The vast majority of the human-introduced uranium has been a relatively recent activity. It started with the atomic age beginning in the 1930’s and escalated after the conclusion of World War II into the Cold War. Still today, more countries are attempting to make nuclear weapons or use nuclear power. These contaminated areas sometimes represent a significant global threat to human and environmental health and safety, demanding a need for remediation or immobilization by non-intrusive methods. Although the contaminating uranium is often depleted in the fissile ²³⁵U and, therefore, does not present a severe radiological risk, but ²³⁸U is still a highly toxic heavy metal [6] . Uranium poisoning affects humans by oxidatively damaging cells causing non-malignant respiratory disease and nephrotoxicity [7] . For the eco-systems at these sites, uranium pre- sents a significant challenge. Although uranium can be adsorbed to roots and be taken up by plants, processes that were initially considered possible remediation strategies, the toxic metal ultimately harms the plant [8] [9] . Similar damage occurs to microbes in that uranium causes oxidative damage to the cell and the DNA. However, despite the high toxicity and potential radiation damage from uranium, some naturally-occurring microbial communities have the ability to survive, and even thrive, in highly contaminated uranium conditions. These capacities yield the desired non-intrusive remediation or immobilization methods [10] [11] .

The ability to persist in a uranium contaminated environment is achieved through a number of different types of bio-transformations, typically chemical transformations of the metal carried out by a microbe. Microbes have been observed reducing, oxidizing, respiring, adsorbing, mineralizing, accumulating or precipitating uranium in the environment [12] . These interactions have been investigated as remediation strategies and in some cases characterized molecularly as unique chemical transformations and electron flow pathways. Microbes of all shapes and sizes have been found to have different interactions with uranium from Proteobacteria to fungi [13] [14] . The widespread nature of the bio- transformations of uranium both geographically and by various microbial families brings into question whether the bio-transformations are biologically or chemically driven? In other words, is any organism in the right redox environment capable of transforming uranium and are there biological advantages to the organisms carrying out these bio-transformations? An open question for researchers in the field has been whether these transformations are detoxification, resistance or just accidents of chemistry?

Previous reviews have discussed uranium reduction [12] , uranium bioremediation methods [13] [15] , uranium geochemistry, mineralization and groundwater transport [3] [16] . While all substantial and important reviews, the previous work has focused only on the most well-known organisms and do not consider the drivers of these processes or the biological benefit to the microbe beyond mentions of possible detoxification. In this review, we expand beyond the more commonly presented reduction and remediation to provide a current list of reported/characterized uranium bio-transformations as defined in Table 1 and schematized in Figure 1 and Figure 2 and to provide a broader but non-ex- haustive list of the organisms that carry out these chemical reactions in Table 2. In Table 3, we provide examples of the chemical reactions of representative uranium bio-transformations. We begin by examining the process of uranium reduction including the organisms, locations, mechanisms and rates. Then, we explore if uranium reduction is a form of cellular respiration or detoxification. In the second section we outline and define additional bio-transformations of uranium that include sorption, bio-markers and nanoparticle synthesis. We conclude by presenting the contributions of classical inorganic chemistry techniques to understanding uranium bio-transformations and by making suggestions about the chemical and biological drivers of this unique and surprising reaction between an actinide that is radioactive and toxic and many naturally-occurring microbes.