Capture of long-missing heme oxygenases that degrade both heme b and heme c.
- 1Institute of Microbiology, College of Life Sciences Zhejiang University Hangzhou China.
- 2State Key Laboratory for Vegetation Structure Function and Construction (VegLab), College of Life Sciences Zhejiang University Hangzhou China.
Abstract
Heme serves as a crucial cofactor for hemoproteins and as an iron reservoir; yet, its accumulation is toxic, necessitating efficient degradation pathways. While the catabolism of free heme b is well characterized, the enzymes that disrupt its counterpart covalently tethered to a peptide (heme c) have remained elusive. Here, through a pipeline of multiple in silico analyses, we predict a distinct Core-only type of heme oxygenases (HOs) within the HugZ superfamily to have the potential to degrade both heme b and peptide-tethered heme c. Biochemical and physiological characterization confirms that representative Core-only-type HOs confer balanced dual-substrate specificity. In contrast, the C-extension and N-fusion-type HOs degrade heme b, but not heme c, because the entry of heme c into the active pocket is blocked by their extra domains. Moreover, we show that the degradation of heme c by the Core-only-type HOs requires proteolytic digestion of heme c-carrying proteins by a protease such as DegQ, which occurs in the periplasm. Overall, this work provides an integrated evolutionary, structural, biochemical, and physiological framework that defines a novel strategy for heme recycling and adaptive metabolic flexibility in bacteria.
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BibTeX
@article{hou2026capture,
title = {{Capture of long-missing heme oxygenases that degrade both heme b and heme c.}},
author = {Jiyuan Hou and Wenhan Dong and Hui Yang and Yuxuan Liang and Haichun Gao},
journal = {MLife},
year = {2026},
month = oct,
doi = {10.1002/mlf2.70118},
url = {https://europepmc.org/article/MED/42953331},
note = {CC BY},
}
RIS
TY - JOUR
TI - Capture of long-missing heme oxygenases that degrade both heme b and heme c.
AU - Jiyuan Hou
AU - Wenhan Dong
AU - Hui Yang
AU - Yuxuan Liang
AU - Haichun Gao
PY - 2026
DA - 2026/10/28
JO - MLife
DO - 10.1002/mlf2.70118
UR - https://europepmc.org/article/MED/42953331
AB - Heme serves as a crucial cofactor for hemoproteins and as an iron reservoir; yet, its accumulation is toxic, necessitating efficient degradation pathways. While the catabolism of free heme b is well characterized, the enzymes that disrupt its counterpart covalently tethered to a peptide (heme c) have remained elusive. Here, through a pipeline of multiple in silico analyses, we predict a distinct Core-only type of heme oxygenases (HOs) within the HugZ superfamily to have the potential to degrade both heme b and peptide-tethered heme c. Biochemical and physiological characterization confirms that representative Core-only-type HOs confer balanced dual-substrate specificity. In contrast, the C-extension and N-fusion-type HOs degrade heme b, but not heme c, because the entry of heme c into the active pocket is blocked by their extra domains. Moreover, we show that the degradation of heme c by the Core-only-type HOs requires proteolytic digestion of heme c-carrying proteins by a protease such as DegQ, which occurs in the periplasm. Overall, this work provides an integrated evolutionary, structural, biochemical, and physiological framework that defines a novel strategy for heme recycling and adaptive metabolic flexibility in bacteria.
SN - 2097-1699
SN - 2770-100X
ER -