An iron (II) dependent oxygenase performs the last missing step of plant lysine catabolism

Thompson, Mitchell G.; Blake-Hedges, Jacquelyn M.; Pereira, J.H.; Belcher, Michael S.; Moore, William M.; Barajas, Jesus F.; Cruz-Morales, Pablo; Washington, Lorenzo; Haushalter, Robert W.; Eiben, Christopher B.; Liu, Yuzhong; Skyrud, Will; Benites, Veronica T.; Barnum, Tyler P.; Baidoo, Edward E. K.; Scheller, Henrik Vibe; Marletta, Michael A.; Shih, Patrick M.; Adams, Paul D.; Keasling, Jay D.

doi:10.1101/2020.01.30.927905

Cited by 2 publications

(1 citation statement)

References 64 publications

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“…We also observed density for chloride, αKG, and a metal between the Fe-binding His149 and His 217 residues. Although iron is the catalytically-relevant metal, we assign the density in the structure as nickel based on our crystallography conditions and precedent for the persistence of nickel during nickel-affinity chromatography of Fe II /αKG-dependent enzymes 73 .…”

Section: Resultsmentioning

confidence: 99%

Regioselective control of biocatalytic C–H activation and halogenation

Kissman¹,

Neugebauer²,

Sumida³

et al. 2022

Preprint

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Biocatalytic C–H activation has the potential to merge enzymatic and synthetic strategies for bond formation. FeII/αKG-dependent halogenases are particularly distinguished for their ability both to control selective C-H activation as well as to direct group transfer of a bound anion along a reaction axis separate from oxygen rebound, enabling the development of new transformations. In this context, we elucidate the basis for selectivity of enzymes that perform selective halogenation to yield 4-Cl-lysine (BesD), 5-Cl-lysine (HalB), and 4-Cl-ornithine (HalD), allowing us to probe how regioselectivity and chain length selectivity are achieved. We now report the crystal structure of the HalB and HalD, revealing the key role of the substrate-lid in positioning the substrate for C4 vs C5 chlorination and recognition of lysine vs ornithine. Targeted engineering of the substrate-binding lid further demonstrates that these selectivities can be altered or switched, showcasing the potential to develop halogenases for biocatalytic applications.

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Section: Resultsmentioning

confidence: 99%

Regioselective control of biocatalytic C–H activation and halogenation

Kissman¹,

Neugebauer²,

Sumida³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

Metabolic functions of misunderstood D-2-hydroxyglutarate

Liu,

Kang,

Zhang

et al. 2024

TIL

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<p>Isocitrate dehydrogenase mutation-induced D-2-hydroxyglutarate (D-2-HG) accumulation may promote the tumorigenesis of numerous cancers. D-2-HG produced by several promiscuous enzymatic reactions under normal conditions is also toxic to organisms. D-2-HG was thus previously viewed as an abnormal metabolite with no physiological function and D-2-HG conversion to 2-ketoglutarate by D-2-HG dehydrogenase seems to be a process of metabolite repair. However, several recent studies have revealed that D-2-HG production is not a meaningless process without a physiological purpose. D-2-HG production actually participates in many core metabolic processes, and disorders of these processes may be the reason for the D-2-HG accumulation in some tumors lacking the isocitrate dehydrogenase mutation. This review summarizes the diverse and widely distributed metabolic processes involving D-2-HG, highlights the physiological functions of D-2-HG generation from various precursors, and discusses the possible applications of enzymes related to D-2-HG metabolism in synthetic biology, diagnosis, and treatment of D-2-HG accumulation-induced diseases.</p>

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An iron (II) dependent oxygenase performs the last missing step of plant lysine catabolism

Cited by 2 publications

References 64 publications

Regioselective control of biocatalytic C–H activation and halogenation

Regioselective control of biocatalytic C–H activation and halogenation

Metabolic functions of misunderstood D-2-hydroxyglutarate

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