Natural Flavins:Occurrence, Role, and Noncanonical Chemistry

Flavoproteins are of key importance to all life on earth for both primary and secondary metabolism. Most flavin-dependent enzymes utilize flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD) as redox cofactor for single-electron and hydride transfer as well as oxidation and oxygenation chemistry at the C4a-locus. Over the last decades, several naturally occurring modified flavins, like 8-formylFAD, F420, and prenylFMN, and covalently bound flavins have been discovered, and were found to further expand the toolbox of flavin chemistry, showcasing extraordinary redox potentials and unprecedented chemistry. Recently, also several examples of “exotic” flavin chemistry, such as N5-oxygenation, have been identified in enzymes that utilize the standard flavins FMN and FAD. It shows that nature has been extremely inventive in exploiting flavins and flavin derivatives as cofactors for an exceptionally wide variety of reactions. Future research will reveal whether other, so far hidden, flavoenzyme-catalyzed chemistries exit.</p

Flavin-Based Catalysis - Preface

Participationincatalyticprocessesisoneofthemainrolesofflavins.Naturehasbeenusing this concept for millions of years. The discovery, description of the structureand function of flavins in the late nineteenth and first half of the twentieth cen-tury has triggered exploitation of the catalytic capabilities of flavins in man-madesynthetic transformations, either using enzymatic or artificial systems. Nowadays,flavins and flavoproteins are enjoying an increased interest from a broad audience,which includes researchers active in synthetic chemistry, enzymology, biocatalysis,and spectroscopy. With new natural flavins still being discovered in recent years,newflavoenzymestructuresandmechanismselucidated,newflavinderivativessyn-thesized, and new photocatalytic and biomimetic approaches developed, it is a verydynamicfieldofresearch.Evenifthemostcommonflavincofactorswerediscoveredabout one century ago, the field is alive and kicking. There are more than 1000 newscientific literature contributions on flavin-related research per year. Many of themare relevant to catalysis. Considering the increasing frequency of new discoveries, one may ask: Are there any limits to flavin catalysis

Modes of Flavin-Based Catalysis

Flavin derivatives participate in various chemical transformations in natural and artificial systems. The unique flavin versatility resulted in the development of many different bio-, organo-, and photocatalytic processes. This chapter draws attention to the ways in which members of the flavin family are involved in catalysis, regardless of whether the reactions take place in enzymes or in artificial catalytic systems. Both light-dependent transformations as well as processes occurring in the absence of light are involved.</p

Flavin-Based Catalysis - Preface

Participationincatalyticprocessesisoneofthemainrolesofflavins.Naturehasbeenusing this concept for millions of years. The discovery, description of the structureand function of flavins in the late nineteenth and first half of the twentieth cen-tury has triggered exploitation of the catalytic capabilities of flavins in man-madesynthetic transformations, either using enzymatic or artificial systems. Nowadays,flavins and flavoproteins are enjoying an increased interest from a broad audience,which includes researchers active in synthetic chemistry, enzymology, biocatalysis,and spectroscopy. With new natural flavins still being discovered in recent years,newflavoenzymestructuresandmechanismselucidated,newflavinderivativessyn-thesized, and new photocatalytic and biomimetic approaches developed, it is a verydynamicfieldofresearch.Evenifthemostcommonflavincofactorswerediscoveredabout one century ago, the field is alive and kicking. There are more than 1000 newscientific literature contributions on flavin-related research per year. Many of themare relevant to catalysis. Considering the increasing frequency of new discoveries, one may ask: Are there any limits to flavin catalysis

Flavin-Based Catalysis - Preface

Participationincatalyticprocessesisoneofthemainrolesofflavins.Naturehasbeenusing this concept for millions of years. The discovery, description of the structureand function of flavins in the late nineteenth and first half of the twentieth cen-tury has triggered exploitation of the catalytic capabilities of flavins in man-madesynthetic transformations, either using enzymatic or artificial systems. Nowadays,flavins and flavoproteins are enjoying an increased interest from a broad audience,which includes researchers active in synthetic chemistry, enzymology, biocatalysis,and spectroscopy. With new natural flavins still being discovered in recent years,newflavoenzymestructuresandmechanismselucidated,newflavinderivativessyn-thesized, and new photocatalytic and biomimetic approaches developed, it is a verydynamicfieldofresearch.Evenifthemostcommonflavincofactorswerediscoveredabout one century ago, the field is alive and kicking. There are more than 1000 newscientific literature contributions on flavin-related research per year. Many of themare relevant to catalysis. Considering the increasing frequency of new discoveries, one may ask: Are there any limits to flavin catalysis

Flavin-Based Catalysis - Preface

Participationincatalyticprocessesisoneofthemainrolesofflavins.Naturehasbeenusing this concept for millions of years. The discovery, description of the structureand function of flavins in the late nineteenth and first half of the twentieth cen-tury has triggered exploitation of the catalytic capabilities of flavins in man-madesynthetic transformations, either using enzymatic or artificial systems. Nowadays,flavins and flavoproteins are enjoying an increased interest from a broad audience,which includes researchers active in synthetic chemistry, enzymology, biocatalysis,and spectroscopy. With new natural flavins still being discovered in recent years,newflavoenzymestructuresandmechanismselucidated,newflavinderivativessyn-thesized, and new photocatalytic and biomimetic approaches developed, it is a verydynamicfieldofresearch.Evenifthemostcommonflavincofactorswerediscoveredabout one century ago, the field is alive and kicking. There are more than 1000 newscientific literature contributions on flavin-related research per year. Many of themare relevant to catalysis. Considering the increasing frequency of new discoveries, one may ask: Are there any limits to flavin catalysis

The vast repertoire of carbohydrate oxidases:An overview

Carbohydrates are widely abundant molecules present in a variety of forms. For their biosynthesis and modification, nature has evolved a plethora of carbohydrate-acting enzymes. Many of these enzymes are of particular interest for biotechnological applications, where they can be used as biocatalysts or biosensors. Among the enzymes catalysing conversions of carbohydrates are the carbohydrate oxidases. These oxidative enzymes belong to different structural families and use different cofactors to perform the oxidation reaction of CH-OH bonds in carbohydrates. The variety of carbohydrate oxidases available in nature reflects their specificity towards different sugars and selectivity of the oxidation site. Thanks to their properties, carbohydrate oxidases have received a lot of attention in basic and applied research, such that nowadays their role in biotechnological processes is of paramount importance. In this review we provide an overview of the available knowledge concerning the known carbohydrate oxidases. The oxidases are first classified according to their structural features. After a description on their mechanism of action, substrate acceptance and characterisation, we report on the engineering of the different carbohydrate oxidases to enhance their employment in biocatalysis and biotechnology. In the last part of the review we highlight some practical applications for which such enzymes have been exploited

Flavin-Based Catalysis - Preface

Participationincatalyticprocessesisoneofthemainrolesofflavins.Naturehasbeenusing this concept for millions of years. The discovery, description of the structureand function of flavins in the late nineteenth and first half of the twentieth cen-tury has triggered exploitation of the catalytic capabilities of flavins in man-madesynthetic transformations, either using enzymatic or artificial systems. Nowadays,flavins and flavoproteins are enjoying an increased interest from a broad audience,which includes researchers active in synthetic chemistry, enzymology, biocatalysis,and spectroscopy. With new natural flavins still being discovered in recent years,newflavoenzymestructuresandmechanismselucidated,newflavinderivativessyn-thesized, and new photocatalytic and biomimetic approaches developed, it is a verydynamicfieldofresearch.Evenifthemostcommonflavincofactorswerediscoveredabout one century ago, the field is alive and kicking. There are more than 1000 newscientific literature contributions on flavin-related research per year. Many of themare relevant to catalysis. Considering the increasing frequency of new discoveries, one may ask: Are there any limits to flavin catalysis

Flavin-Based Catalysis - Preface

Participationincatalyticprocessesisoneofthemainrolesofflavins.Naturehasbeenusing this concept for millions of years. The discovery, description of the structureand function of flavins in the late nineteenth and first half of the twentieth cen-tury has triggered exploitation of the catalytic capabilities of flavins in man-madesynthetic transformations, either using enzymatic or artificial systems. Nowadays,flavins and flavoproteins are enjoying an increased interest from a broad audience,which includes researchers active in synthetic chemistry, enzymology, biocatalysis,and spectroscopy. With new natural flavins still being discovered in recent years,newflavoenzymestructuresandmechanismselucidated,newflavinderivativessyn-thesized, and new photocatalytic and biomimetic approaches developed, it is a verydynamicfieldofresearch.Evenifthemostcommonflavincofactorswerediscoveredabout one century ago, the field is alive and kicking. There are more than 1000 newscientific literature contributions on flavin-related research per year. Many of themare relevant to catalysis. Considering the increasing frequency of new discoveries, one may ask: Are there any limits to flavin catalysis

Production of indigo through the use of a dual-function substrate and a bifunctional fusion enzyme

The current chemical process for industrial indigo production puts a heavy burden on the environment. An attractive option would be to develop an alternative biotechnological process which does not rely on a petrochemical. This study describes a new biotransformation approach in which l-tryptophan is used as starting material. Its conversion to indigo can be achieved through recombinant overexpression of a bifunctional fusion enzyme, flavin-containing monooxygenase (FMO) fused to tryptophanase (TRP). First, TRP converts l-tryptophan into pyruvate, ammonia and indole. The formed indole serves as substrate for FMO, resulting in indigo formation, while pyruvate fuels the cells for regenerating the required NADPH. To optimize this bioconversion, different fusion constructs were tested. Fusing TRP to FMO at either the N-terminus (TRP-FMO) or the C-terminus (FMO-TRP) resulted in similar high expression levels of bifunctional fusion enzymes. Using whole cells and l-tryptophan as a precursor, high production levels of indigo could be obtained, significantly higher when compared with cells containing only overexpressed FMO. The TRP-FMO containing cells gave the highest yield of indigo resulting in full conversion of 2.0 g l-tryptophan into 1.7 g indigo per liter of culture. The process developed in this study provides an alternative biotransformation approach for the production of indigo starting from biobased starting material