Porphyrin driven redox tuning in structurally defined de novo heme proteins

Authors

Mellor, C., Williams, C., Bungay, E. L., Berrones-Reyes, J. C., Barringer, R., Back, C., Molinaro, P., Koder, R. L., Lichtenstein, B. R., Mulholland, A. J., Crump, M. P., Anderson, R. J.

Abstract

Designing redox proteins with predictable and tuneable electron transfer properties is a major goal in de novo bioenergetics. Here we show that replacing heme B with a series of structurally conservative non natural metalloporphyrins enables broad modulation of redox potentials over 400 mV in the de novo designed monoheme m4D2 and diheme 4D2 T19D. The non-natural porphyrins bind with high affinity and do not compromise either the heme binding site or global protein structure, as evidenced by X-ray crystallography and NMR spectroscopy. We also report the native-like NMR structure of m4D2 loaded with the non-natural and symmetric iron 2,4-dimethyldeuteroporphyrin IX, confirming our modular approach to tetrahelical redox protein design. This work establishes a versatile platform for constructing tuneable electron carriers for engineered bioenergetic pathways and bioelectronic applications.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 11 Jun 2026.

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