Microbial interactions with Pb2+ in the environment are not well understood. The literature includes several reports of bacteria precipitating Pb2+ to an insoluble brown compound. Our laboratory has revealed the identity of this compound to be Pb9(PO4)6. This result in noteworthy because lead phosphate salt because it cannot be synthesized in the laboratory at temperatures below 200°C, yet it can be generated by a wide array of microbes cultured at or near room temperature. Understanding the mechanism behind microbial lead precipitation may reveal a novel catalysis and shed light on how microorganisms interact with lead in the environment. Genetic analysis of mutants with altered lead precipitation phenotypes should identify cellular components important in regulating and carrying out lead precipitation. Previous work in our laboratory has focused on Vibrio harveyi, and has demonstrated that previously unidentified quorum sensing systems can regulate lead precipitation. Currently we are using Caulobacter crescentus as a model organism. Genetic analysis of Caulobacter mutants reveals that a region containing β/γ crystallin homologs and an S-layer gene cluster represents a hotspot for mutations that confer a hyper-precipitation phenotype. This observation suggests that integrity of the S-layer is not conducive for lead phosphate precipitation, and that the substrate of the precipitation reaction requires contact with cellular components interior to the S-layer. A strategy for identifying and mapping additional important loci in Caulobacter outside the S-layer gene cluster will also be presented.