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Biosynthesis and Insertion of Heme

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Aerobic Utilization of Hydrocarbons, Oils, and Lipids

Abstract

The red, iron containing tetrapyrrole heme is an essential cofactor of enzymes involved in the electron transport chain of energy generation and used for catalyzing chemically challenging reactions of the metabolism. It is also used for diatomic gas transport (O2, CO, CO2, NO, N2O), catalysis, and detection. Multiple transcriptional regulators and transporters bind heme. This chapter focuses on the highly unusual pathways for heme biosynthesis and the integration of protoheme into target proteins. Today, three different biosynthetic routes for heme formation are known. The general precursor molecule of all tetrapyrroles 5-aminolevulinic acid is formed by two different pathways starting either with glutamyl-tRNA or succinyl-CoA and glycine. The conversion of 5-aminolevulinic acid to uroporphyrinogen III is common to all biosynthetic paths. Then the pathway branches to a classical route via protoporphyrin and two currently known alternative routes via coproporpyhrin III and siroheme. Various steps are catalyzed by up to three structurally unrelated enzymes. Finally, formed protoheme (heme b) gets actively inserted into proteins by the “Radical SAM” protein HemW. A detailed description of involved intermediates, enzymes, and their mechanisms are depicted below.

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Acknowledgments

We thank Stefan Barthels for his excellent technical assistance and are indebted to the Deutsche Forschungsgemeinschaft (GRK 2223, PROCOMPAS) for funding.

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Müller, K., Mingers, T., Haskamp, V., Jahn, D., Jahn, M. (2019). Biosynthesis and Insertion of Heme. In: Rojo, F. (eds) Aerobic Utilization of Hydrocarbons, Oils, and Lipids. Handbook of Hydrocarbon and Lipid Microbiology . Springer, Cham. https://doi.org/10.1007/978-3-319-50418-6_17

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