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Journal ArticleDOI

TerC Is a Multifunctional and Promiscuous Flavoprotein Monooxygenase That Catalyzes Bimodal Oxidative Transformations.

06 Nov 2021-Organic Letters (American Chemical Society (ACS))-Vol. 23, Iss: 22, pp 8947-8951
TL;DR: This paper demonstrated bimodal reaction cascades and advanced the biosynthetic knowledge of fungal cyclopentenes, this work also set the stage for the bioengineering of 6-HM polyketides.
About: This article is published in Organic Letters.The article was published on 2021-11-06 and is currently open access. It has received 4 citations till now.
Citations
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Journal ArticleDOI
TL;DR: This review introduces the mechanisms for different FMOs, with the classical FAD (C4a)-hydroperoxide as the major oxidant, and summarizes the difference between F MOs and cytochrome P450 (CYP450) monooxygenases emphasizing the advantages of FMO's and their specificity for substrates.
Abstract: Natural products are usually highly complicated organic molecules with special scaffolds, and they are an important resource in medicine. Natural products with complicated structures are produced by enzymes, and this is still a challenging research field, its mechanisms requiring detailed methods for elucidation. Flavin adenine dinucleotide (FAD)-dependent monooxygenases (FMOs) catalyze many oxidation reactions with chemo-, regio-, and stereo-selectivity, and they are involved in the synthesis of many natural products. In this review, we introduce the mechanisms for different FMOs, with the classical FAD (C4a)-hydroperoxide as the major oxidant. We also summarize the difference between FMOs and cytochrome P450 (CYP450) monooxygenases emphasizing the advantages of FMOs and their specificity for substrates. Finally, we present examples of FMO-catalyzed synthesis of natural products. Based on these explanations, this review will expand our knowledge of FMOs as powerful enzymes, as well as implementation of the FMOs as effective tools for biosynthesis.

8 citations

Journal ArticleDOI
TL;DR: Zhang et al. as mentioned in this paper summarized the representative studies on the biosynthesis of fungal secondary metabolites by gene knockout and heterologous expression under the fungal genome mining in the last three years.
Abstract: The in-depth study of fungal secondary metabolites (SMs) over the past few years has led to the discovery of a vast number of novel fungal SMs, some of which possess good biological activity. However, because of the limitations of the traditional natural product mining methods, the discovery of new SMs has become increasingly difficult. In recent years, with the rapid development of gene sequencing technology and bioinformatics, new breakthroughs have been made in the study of fungal SMs, and more fungal biosynthetic gene clusters of SMs have been discovered, which shows that the fungi still have a considerable potential to produce SMs. How to study these gene clusters to obtain a large number of unknown SMs has been a research hotspot. With the continuous breakthrough of molecular biology technology, gene manipulation has reached a mature stage. Methods such as gene knockout and heterologous expression techniques have been widely used in the study of fungal SM biosynthesis and have achieved good effects. In this review, the representative studies on the biosynthesis of fungal SMs by gene knockout and heterologous expression under the fungal genome mining in the last three years were summarized. The techniques and methods used in these studies were also briefly discussed. In addition, the prospect of synthetic biology in the future under this research background was proposed.

3 citations

Journal ArticleDOI
TL;DR: In this paper , an NADPH/FAD-dependent monooxygenase VibO was identified as the key enzyme performing a crucial ringexpansive oxygenation on the phenol ring to generate the oxepin-2-one structure of 3 .
Abstract: Abstract Oxepinone rings represent one of structurally unusual motifs of natural products and the biosynthesis of oxepinones is not fully understood. 1,5- Seco -vibralactone ( 3 ) features an oxepinone motif and is a stable metabolite isolated from mycelial cultures of the mushroom Boreostereum vibrans . Cyclization of 3 forms vibralactone ( 1 ) whose β-lactone-fused bicyclic core originates from 4-hydroxybenzoate, yet it remains elusive how 4-hydroxybenzoate is converted to 3 especially for the oxepinone ring construction in the biosynthesis of 1 . In this work, using activity-guided fractionation together with proteomic analyses, we identify an NADPH/FAD-dependent monooxygenase VibO as the key enzyme performing a crucial ring-expansive oxygenation on the phenol ring to generate the oxepin-2-one structure of 3 . The crystal structure of VibO reveals that it forms a dimeric phenol hydroxylase-like architecture featured with a unique substrate-binding pocket adjacent to the bound FAD. Computational modeling and solution studies provide insight into the likely VibO active site geometry, and suggest possible involvement of a flavin-C4a-OO(H) intermediate.
Journal ArticleDOI
TL;DR: This paper reported the isolation of fumimycin and a related new racemic compound named lentofuranine from Aspergillus section Fumigati, which was assembled by a nonenzymatic condensation of a polyketide intermediate from the terrein biosynthetic pathway and a highly reactive azlactone intermediate produced by an unrelated nonribosomal peptide synthetase carrying a terminal condensation-like domain.
Abstract: Pathogenic fungi of Aspergillus section Fumigati are known to produce various secondary metabolites. A reported isolation of a compound with an atypical carbon skeleton called fumimycin from A. fumisynnematus prompted us to examine a related fungus, A. lentulus, for production of similar products. Here we report the isolation of fumimycin and a related new racemic compound we named lentofuranine. Detailed analyses revealed that both compounds were assembled by a nonenzymatic condensation of a polyketide intermediate from the terrein biosynthetic pathway and a highly reactive azlactone intermediate produced by an unrelated nonribosomal peptide synthetase carrying a terminal condensation-like domain. While highly reactive azlactone is commonly used in chemical synthesis, its production by a conventional non-metalloenzyme and employment as a biosynthetic pathway intermediate is unprecedented. The observed unusual carbon skeleton formation is likely due to the reactivity of azlactone. Our finding provides another example of a chemical principle being aptly exploited by a biological system.
References
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Journal ArticleDOI
TL;DR: An inventory of known flavoprotein monooxygenases belonging to these different enzyme subclasses is provided and the biocatalytic potential of a selected number of flavop protein monooxyGENases is highlighted.

612 citations

Journal ArticleDOI
TL;DR: This review attempts to provide descriptive information on the enzymes from various microorganisms involved in the biodegradation of wide range of pollutants, applications, and suggestions required to overcome the limitations of their efficient use.
Abstract: A large number of enzymes from bacteria, fungi, and plants have been reported to be involved in the biodegradation of toxic organic pollutants. Bioremediation is a cost effective and nature friendly biotechnology that is powered by microbial enzymes. The research activity in this area would contribute towards developing advanced bioprocess technology to reduce the toxicity of the pollutants and also to obtain novel useful substances. The information on the mechanisms of bioremediation-related enzymes such as oxido-reductases and hydrolases have been extensively studied. This review attempts to provide descriptive information on the enzymes from various microorganisms involved in the biodegradation of wide range of pollutants, applications, and suggestions required to overcome the limitations of their efficient use.

580 citations

Journal ArticleDOI
TL;DR: An update of the classification of flavin-dependent monooxygenases is presented and the latest advances in the understanding of their catalytic and structural properties are summarized.

395 citations

Journal ArticleDOI
TL;DR: From a marine-derived strain of the fungus Emericella variecolor, varitriol (1), varioxirane (2), dihydroterrein (3), and varixanthone (4), besides the known mold metabolites ergosterol, terrein, shamixanth one, and tajIXanthone hydrate, were identified.
Abstract: From a marine-derived strain of the fungus Emericella variecolor, varitriol (1), varioxirane (2), dihydroterrein (3), and varixanthone (4), besides the known mold metabolites ergosterol, terrein, shamixanthone, and tajixanthone hydrate, were identified. The chemical structures of 1-4 were established by means of spectroscopic techniques and some chemical transformations. In the NCI's 60-cell panel, varitriol (1) displayed increased potency toward selected renal, CNS, and breast cancer cell lines. Varixanthone (4) showed antimicrobial activity.

153 citations

Journal ArticleDOI
TL;DR: MtmOIV, the key oxygenase of the mithramycin biosynthetic pathway in Streptomyces argillaceus, was proven to act initially as Baeyer-Villiger monooxygenase, but may also catalyze various follow-up reaction steps.
Abstract: MtmOIV, the key oxygenase of the mithramycin biosynthetic pathway in Streptomyces argillaceus, was proven to act initially as Baeyer-Villiger monooxygenase, but may also catalyze various follow-up reaction steps. The reaction of the overexpressed pure His6-tagged enzyme with its substrate premithramycin B was studied. Various intermediates and products were isolated and physicochemically characterized, several of them being previously unknown compounds. This is the first example in which a bacterial enzyme was unequivocally proven to act as Baeyer-Villigerase with its natural substrate, that is, in its natural context.

115 citations

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