The Phylogeny of Class B Flavoprotein Monooxygenases and the Origin of the YUCCA Protein Family

Turnaev, I. I.; Gunbin, Konstantin; Суслов, В. В.; Akberdin, Ilya R.; Kolchanov, Nikolay А.; Afonnikov, D. A.

doi:10.3390/plants9091092

Cited by 5 publications

(4 citation statements)

References 76 publications

(110 reference statements)

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“…In the observed structure, the active site appears completely inaccessible, except for the NADPH binding site, where a cavity grants the NAD( P )H to reach the flavin. In BVMOs and NMOs (recently inserted in the same phylogenetic group of type II FMOs), the NAD(P) + occupies this pocket for the complete catalytic cycle; , therefore, it is very likely that the substrate enters the active site on a different way. A triangular-shaped helical structure (residues 370–434) appears to create an opening to the active site (Figure ).…”

Section: Resultsmentioning

confidence: 99%

A Cold-Active Flavin-Dependent Monooxygenase from Janthinobacterium svalbardensis Unlocks Applications of Baeyer–Villiger Monooxygenases at Low Temperature

et al. 2023

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Cold-active enzymes maintain a large part of their optimal activity at low temperatures. Therefore, they can be used to avoid side reactions and preserve heat-sensitive compounds. Baeyer–Villiger monooxygenases (BVMO) utilize molecular oxygen as a co-substrate to catalyze reactions widely employed for steroid, agrochemical, antibiotic, and pheromone production. Oxygen has been described as the rate-limiting factor for some BVMO applications, thereby hindering their efficient utilization. Considering that oxygen solubility in water increases by 40% when the temperature is decreased from 30 to 10 °C, we set out to identify and characterize a cold-active BVMO. Using genome mining in the Antarctic organism Janthinobacterium svalbardensis, a cold-active type II flavin-dependent monooxygenase (FMO) was discovered. The enzyme shows promiscuity toward NADH and NADPH and high activity between 5 and 25 °C. The enzyme catalyzes the monooxygenation and sulfoxidation of a wide range of ketones and thioesters. The high enantioselectivity in the oxidation of norcamphor (eeS = 56%, eeP > 99%, E > 200) demonstrates that the generally higher flexibility observed in the active sites of cold-active enzymes, which compensates for the lower motion at cold temperatures, does not necessarily reduce the selectivity of these enzymes. To gain a better understanding of the unique mechanistic features of type II FMOs, we determined the structure of the dimeric enzyme at 2.5 Å resolution. While the unusual N-terminal domain has been related to the catalytic properties of type II FMOs, the structure shows a SnoaL-like N-terminal domain that is not interacting directly with the active site. The active site of the enzyme is accessible only through a tunnel, with Tyr-458, Asp-217, and His-216 as catalytic residues, a combination not observed before in FMOs and BVMOs.

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Section: Resultsmentioning

confidence: 99%

A Cold-Active Flavin-Dependent Monooxygenase from Janthinobacterium svalbardensis Unlocks Applications of Baeyer–Villiger Monooxygenases at Low Temperature

et al. 2023

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“…The adjacent KS 0 domain is then hypothesized to shuttle the glycine thioester to the OxiC ACP domain where the OX domain of OxiB oxidizes the glycine amino group to the corresponding oxime via a hydroxylamine and nitroso intermediate. Sequence alignments and phylogenetic analysis revealed that the OX domain belongs to the class B flavoprotein monooxygenases (FMOs) which contain two Rossman folds, one for the binding of FAD and one for NADPH, as well as a characteristic FMO sequence motif (FxGxxxHxxxY) (Figure S33A) [29, 30] . Within the class B FMOs, the OxiB OX domain groups together with the corresponding domains from the necroxime and lobatamide pathways in a separate clade within the type I FMO subclass (Figure S34).…”

Section: Resultsmentioning

confidence: 99%

“…Sequence alignments and phylogenetic analysis revealed that the OX domain belongs to the class B flavoprotein monooxygenases (FMOs) which contain two Rossman folds, one for the binding of FAD and one for NADPH, as well as a characteristic FMO sequence motif (FxGxxxHxxxY) (Figure S33A). [29,30] Within the class B FMOs, the OxiB OX domain groups together with the corresponding domains from the necroxime and lobatamide pathways in a separate clade within the type I FMO subclass (Figure S34). Following oxime formation, a second KS 0 domain appended to the N-terminus of OxiD likely transfers the intermediate to the ACP domain within OxiE.…”

Section: The Oxib Ox and The Oxid Mt Domain Are Involved In Omethylox...mentioning

confidence: 99%

Polyketide Synthase‐Mediated O‐Methyloxime Formation in the Biosynthesis of the Oximidine Anticancer Agents

Vriens,

De Ruysscher,

Weir

et al. 2023

Angewandte Chemie

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Bacterial trans‐acyltransferase polyketide synthases (trans‐AT PKSs) are modular megaenzymes that employ unusual catalytic domains to assemble diverse bioactive natural products. One such PKS is responsible for the biosynthesis of the oximidine anticancer agents, oxime‐substituted benzolactone enamides that inhibit vacuolar H+‐ATPases. Here, we describe the identification of the oximidine gene cluster in Pseudomonas baetica and the characterization of four novel oximidine variants, including a structurally simpler intermediate that retains potent anticancer activity. Using a combination of in vivo, in vitro and computational approaches, we experimentally elucidate the oximidine biosynthetic pathway and reveal an unprecedented mechanism for O‐methyloxime formation. We show that this process involves a specialized monooxygenase and methyltransferase domain and provide insight into their activity, mechanism and specificity. Our findings expand the catalytic capabilities of trans‐AT PKSs and identify potential strategies for the production of novel oximidine analogues.

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“…Although YUCCA flavin monooxygenases were proposed to exist in Chlorophytes (Khasin et al 2018), charophytes (Wang et al 2014), and brown algae (Bogaert et al 2019), exhaustive phylogenetic (Yue et al 2012(Yue et al , 2014Bowman et al 2017;Turnaev et al 2020), and sequence similarity network analysis (Dai et al 2013) indicate YUCCA flavin monooxygenases are a land plant innovation acquired by horizontal gene transfer from bacteria. Thus, if charophyte TAR genes can produce IPyA, IPyA may have had an IAA-independent function in the algal ancestor.…”

Section: Origin and Evolution Of The Components Auxin Biosynthesismentioning

confidence: 99%

On the Evolutionary Origins of Land Plant Auxin Biology

Bowman

Flores-Sandoval

Kato

2021

Cold Spring Harb Perspect Biol

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The Phylogeny of Class B Flavoprotein Monooxygenases and the Origin of the YUCCA Protein Family

Cited by 5 publications

References 76 publications

A Cold-Active Flavin-Dependent Monooxygenase from Janthinobacterium svalbardensis Unlocks Applications of Baeyer–Villiger Monooxygenases at Low Temperature

A Cold-Active Flavin-Dependent Monooxygenase from Janthinobacterium svalbardensis Unlocks Applications of Baeyer–Villiger Monooxygenases at Low Temperature

Polyketide Synthase‐Mediated O‐Methyloxime Formation in the Biosynthesis of the Oximidine Anticancer Agents

On the Evolutionary Origins of Land Plant Auxin Biology

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