| Autor: |
Carlson HK; Energy Biosciences Institute, University of California, Berkeley , Berkeley, California 94720, United States.; Physical Biosciences Division, Lawrence Berkeley National Lab , Berkeley, California 94720, United States., Mullan MR; Energy Biosciences Institute, University of California, Berkeley , Berkeley, California 94720, United States., Mosqueda LA; Energy Biosciences Institute, University of California, Berkeley , Berkeley, California 94720, United States., Chen S; Small Molecule Discovery Center, University of California, San Francisco , San Francisco, California 94143, United States., Arkin MR; Small Molecule Discovery Center, University of California, San Francisco , San Francisco, California 94143, United States., Coates JD; Energy Biosciences Institute, University of California, Berkeley , Berkeley, California 94720, United States.; Earth Sciences Division, Lawrence Berkeley National Laboratory , Berkeley, California 94720, United States.; Department of Plant and Microbial Biology, University of California, Berkeley , Berkeley, California 94720, United States. |
| Abstrakt: |
The selective perturbation of complex microbial ecosystems to predictably influence outcomes in engineered and industrial environments remains a grand challenge for geomicrobiology. In some industrial ecosystems, such as oil reservoirs, sulfate reducing microorganisms (SRM) produce hydrogen sulfide which is toxic, explosive, and corrosive. Despite the economic cost of sulfidogenesis, there has been minimal exploration of the chemical space of possible inhibitory compounds, and very little work has quantitatively assessed the selectivity of putative souring treatments. We have developed a high-throughput screening strategy to identify potent and selective inhibitors of SRM, quantitatively ranked the selectivity and potency of hundreds of compounds and identified previously unrecognized SRM selective inhibitors and synergistic interactions between inhibitors. Zinc pyrithione is the most potent inhibitor of sulfidogenesis that we identified, and is several orders of magnitude more potent than commonly used industrial biocides. Both zinc and copper pyrithione are also moderately selective against SRM. The high-throughput (HT) approach we present can be readily adapted to target SRM in diverse environments and similar strategies could be used to quantify the potency and selectivity of inhibitors of a variety of microbial metabolisms. Our findings and approach are relevant to efforts to engineer environmental ecosystems and also to understand the role of natural gradients in shaping microbial niche space. |
