Discovery of Hydroxylase Activity for PqqB Provides a Missing Link in the Pyrroloquinoline Quinone Biosynthetic Pathway

Eric M. Koehn, John A. Latham, Tara Armand, Robert L Evans, Xiongying Tu, Carrie M Wilmot, Anthony T. Iavarone, Judith P. Klinman

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Understanding the biosynthesis of cofactors is fundamental to the life sciences, yet to date a few important pathways remain unresolved. One example is the redox cofactor pyrroloquinoline quinone (PQQ), which is critical for C1 metabolism in many microorganisms, a disproportionate number of which are opportunistic human pathogens. While the initial and final steps of PQQ biosynthesis, involving PqqD/E and PqqC, have been elucidated, the precise nature and order of the remaining transformations in the pathway are unknown. Here we show evidence that the remaining essential biosynthetic enzyme PqqB is an iron-dependent hydroxylase catalyzing oxygen-insertion reactions that are proposed to produce the quinone moiety of the mature PQQ cofactor. The demonstrated reactions of PqqB are unprecedented within the metallo β-lactamase protein family and expand the catalytic repertoire of nonheme iron hydroxylases. These new findings also generate a nearly complete description of the PQQ biosynthetic pathway.

Original languageEnglish (US)
Pages (from-to)4398-4405
Number of pages8
JournalJournal of the American Chemical Society
Volume141
Issue number10
DOIs
StatePublished - Mar 13 2019

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PQQ Cofactor
Biosynthesis
Biosynthetic Pathways
Mixed Function Oxygenases
Iron
Pathogens
Metabolism
Microorganisms
Enzymes
Proteins
Oxygen
Biological Science Disciplines
Oxidation-Reduction

Cite this

Discovery of Hydroxylase Activity for PqqB Provides a Missing Link in the Pyrroloquinoline Quinone Biosynthetic Pathway. / Koehn, Eric M.; Latham, John A.; Armand, Tara; Evans, Robert L; Tu, Xiongying; Wilmot, Carrie M; Iavarone, Anthony T.; Klinman, Judith P.

In: Journal of the American Chemical Society, Vol. 141, No. 10, 13.03.2019, p. 4398-4405.

Research output: Contribution to journalArticle

Koehn, Eric M. ; Latham, John A. ; Armand, Tara ; Evans, Robert L ; Tu, Xiongying ; Wilmot, Carrie M ; Iavarone, Anthony T. ; Klinman, Judith P. / Discovery of Hydroxylase Activity for PqqB Provides a Missing Link in the Pyrroloquinoline Quinone Biosynthetic Pathway. In: Journal of the American Chemical Society. 2019 ; Vol. 141, No. 10. pp. 4398-4405.
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