Deciphering the assembly process of PQQ dependent methanol dehydrogenase
Haichuan Zhou,
Junqing Sun,
Jian Cheng,
Min Wu,
Jie Bai,
Qian Li,
Jie Shen,
Manman Han,
Chen Yang,
Liangpo Li,
Yuwan Liu,
Qichen Cao,
Weidong Liu,
Haixia Xiao,
Hongjun Dong (),
Feng Gao () and
Huifeng Jiang ()
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Haichuan Zhou: Chinese Academy of Sciences
Junqing Sun: Zhejiang University School of Medicine
Jian Cheng: Chinese Academy of Sciences
Min Wu: Chinese Academy of Sciences
Jie Bai: Chinese Academy of Sciences
Qian Li: Chinese Academy of Sciences
Jie Shen: Chinese Academy of Sciences
Manman Han: Chinese Academy of Sciences
Chen Yang: Chinese Academy of Sciences
Liangpo Li: Chinese Academy of Sciences
Yuwan Liu: Chinese Academy of Sciences
Qichen Cao: Chinese Academy of Sciences
Weidong Liu: Chinese Academy of Sciences
Haixia Xiao: Chinese Academy of Sciences
Hongjun Dong: Chinese Academy of Sciences
Feng Gao: Chinese Academy of Sciences
Huifeng Jiang: Chinese Academy of Sciences
Nature Communications, 2025, vol. 16, issue 1, 1-11
Abstract:
Abstract Pyrroloquinoline quinone (PQQ)-dependent methanol dehydrogenases (MDHs), the periplasmic metalloenzymes in Gram-negative methylotrophic bacteria, play a pivotal role in methane and methanol bio-utilization. Although the structures of many PQQ-dependent MDHs have been resolved, including the canonical heterotetrameric enzymes composed of two MxaF and two MxaI subunits with a molecule of PQQ and a calcium ion in the active site in MxaF, the biogenesis of these enzymes remains elusive. Here, we characterize a chaperone, MxaJ, responsible for PQQ incorporation by reconstructing a PQQ-dependent MDH assembly system in Escherichia coli. Using cryo-electron microscopy, we capture the structures of the intermediate complexes formed by the chaperone MxaJ and catalytic subunit MxaF during PQQ-dependent MDH maturation, revealing a chaperone-mediated molecular mechanism of cofactor incorporation. These findings not only advance our understanding on the biogenesis of PQQ-dependent MDH, but also provide an alternative engineering way for methane and methanol bioconversion.
Date: 2025
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DOI: 10.1038/s41467-025-61958-w
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