Abstract
Iron is a vital mineral for almost all living organisms and has a pivotal role in central metabolism. Despite its great abundance on earth, the accessibility for microorganisms is often limited, because poorly soluble ferric iron (Fe3+) is the predominant oxidation state in an aerobic environment. Hence, the reduction of Fe3+ is of essential importance to meet the cellular demand of ferrous iron (Fe2+) but might become detrimental as excessive amounts of intracellular Fe2+ tend to undergo the cytotoxic Fenton reaction in the presence of hydrogen peroxide. We demonstrate that the complex formation rate of Fe3+ and phenolic compounds like protocatechuic acid was increased by 46% in the presence of HCO3- and thus accelerated the subsequent redox reaction, yielding reduced Fe2+ Consequently, elevated CO2/HCO3- levels increased the intracellular Fe2+ availability, which resulted in at least 50% higher biomass-specific fluorescence of a DtxR-based Corynebacterium glutamicum reporter strain, and stimulated growth. Since the increased Fe2+ availability was attributed to the interaction of HCO3- and chemical iron reduction, the abiotic effect postulated in this study is of general relevance in geochemical and biological environments.IMPORTANCE In an oxygenic environment, poorly soluble Fe3+ must be reduced to meet the cellular Fe2+ demand. This study demonstrates that elevated CO2/HCO3- levels accelerate chemical Fe3+ reduction through phenolic compounds, thus increasing intracellular Fe2+ availability. A number of biological environments are characterized by the presence of phenolic compounds and elevated HCO3- levels and include soil habitats and the human body. Fe2+ availability is of particular interest in the latter, as it controls the infectiousness of pathogens. Since the effect postulated here is abiotic, it generally affects the Fe2+ distribution in nature.
Highlights
Iron is a vital mineral for almost all living organisms and has a pivotal role in central metabolism
Since reduced Fe2ϩ is incorporated as a prosthetic group in a number of enzymes that belong to respiratory complexes or that participate in tricarboxylic acid (TCA) cycle reactions and stress response inside the cell, the reduction of Fe3ϩ is of central relevance
To monitor intracellular Fe2ϩ availability, we constructed the fluorescence-based reporter strain C. glutamicum FEM3 which responds to the activation state of DtxR
Summary
Iron is a vital mineral for almost all living organisms and has a pivotal role in central metabolism. We demonstrate that the complex formation rate of Fe3ϩ and phenolic compounds like protocatechuic acid was increased by 46% in the presence of HCO3Ϫ and accelerated the subsequent redox reaction, yielding reduced Fe2ϩ. Since the increased Fe2ϩ availability was attributed to the interaction of HCO3Ϫ and chemical iron reduction, the abiotic effect postulated in this study is of general relevance in geochemical and biological environments. This study demonstrates that elevated CO2/HCO3Ϫ levels accelerate chemical Fe3ϩ reduction through phenolic compounds, increasing intracellular Fe2ϩ availability. It turned out that most designated ferric reductases are flavin reductases that regenerate the substrate for chemical iron reduction This is not limited to intracellular reactions, since it was shown recently that the human pathogen Listeria monocytogenes possesses an extracellular electron transfer apparatus, in which iron reduction is mediated by flavin [5]. To ensure sufficient initial iron uptake, PCA became a component of the widely used CgXII medium [10]
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