Development Of Biocatalysis Research Articles

Pickering Emulsions Biocatalysis: Recent Developments and Emerging Trends.

Biocatalysis within biphasic systems is gaining significant attention in the field of synthetic chemistry, primarily for its ability to solve the problem of incompatible solubilities between biocatalysts and organic compounds. By forming an emulsion from these two-phase systems, a larger surface area is created, which greatly improves the mass transfer of substrates to the biocatalysts. Among the various types of emulsions, Pickering emulsions stand out due to their excellent stability, compatibility with biological substances, and the ease with which they can be formed and separated. This makes them ideal for reusing both the emulsifiers and the biocatalysts. This review explores the latest developments in biocatalysis using Pickering emulsions. It covers the structural features, methods of creation, innovations in flow biocatalysis, and the role of interfaces in these processes. Additionally, the challenges and future directions are discussed in combining chemical and biological catalysts within Pickering emulsion frameworks to advance synthetic methodologies.

Immobilization of enzymes on polymers with upper critical solution temperature: promising engineering of enzymes for biocatalysis

A review of the developments in biocatalysis using upper critical solution temperature (UCST)-type polymer-immobilized enzymes.

Recent developments in the enzymatic modifications of steroid scaffolds.

Steroids are an important family of bioactive compounds. Steroid drugs are renowned for their multifaceted pharmacological activities and are the second-largest category in the global pharmaceutical market. Recent developments in biocatalysis and biosynthesis have led to the increased use of enzymes to enhance the selectivity, efficiency, and sustainability for diverse modifications of steroids. This review discusses the advancements achieved over the past five years in the enzymatic modifications of steroid scaffolds, focusing on enzymatic hydroxylation, reduction, dehydrogenation, cascade reactions, and other modifications for future research on the synthesis of novel steroid compounds and related drugs, and new therapeutic possibilities.

A Career in Biocatalysis: Kurt Faber

Kurt Faber, a synthetic organic chemist by training, strongly influenced the field of biocatalysis throughout the course of his four-decade career (from the late 1980s to the early 2020s). The evolution of his career has gone hand in hand with the development of biocatalysis into a mature and versatile discipline originally deep-rooted in organic chemistry that quickly integrated techniques from molecular biology. His work has provided numerous grounds for recognizing natural catalysts as essential tools in organic synthesis, complementing the more chemical approaches. An important aspect of Kurt Faber’s career encompasses teaching, mentoring, and encouraging the development of younger scientists worldwide. His book, Biotransformations in Organic Chemistry, now in its seventh edition, has become a recognized tool for training generations of chemists and biotechnologists and remains a reference worldwide. At Biotrans 2021, the 15th International Symposium on Biocatalysis and Biotransformations (originally scheduled to be held in Graz, Austria, and eventually held online due to the COVID-19 pandemic), Kurt Faber received the Biotrans senior award in recognition of his innovative contributions to the field. In this Account, we would like to acknowledge his contributions to the field of biocatalysis, highlighting both the growing importance of this discipline in many (industrial) sectors and the profound changes that have occurred in recent decades, while reflecting on some of Kurt Faber’s most important discoveries and his legacy to this field.

Chemoenzymatic Total Synthesis of Natural Products.

The total synthesis of structurally complex natural products has challenged and inspired generations of chemists and remains an exciting area of active research. Despite their history as privileged bioactivity-rich scaffolds, the use of natural products in drug discovery has waned. This shift is driven by their relatively low abundance hindering isolation from natural sources and the challenges presented by their synthesis. Recent developments in biocatalysis have resulted in the application of enzymes for the construction of complex molecules. From the inception of the Narayan lab in 2015, we have focused on harnessing the exquisite selectivity of enzymes alongside contemporary small molecule-based approaches to enable concise chemoenzymatic routes to natural products.We have focused on enzymes from various families that perform selective oxidation reactions. For example, we have targeted xyloketal natural products through a strategy that relies on a chemo- and site-selective biocatalytic hydroxylation. Members of the xyloketal family are characterized by polycyclic ketal cores and demonstrate potent neurological activity. We envisioned assembling a representative xyloketal natural product (xyloketal D) involving a biocatalytically generated ortho-quinone methide intermediate. The non-heme iron (NHI) dependent monooxygenase ClaD was used to perform the benzylic hydroxylation of a resorcinol precursor, the product of which can undergo spontaneous loss of water to form an ortho-quinone methide under mild conditions. This intermediate was trapped using a chiral dienophile to complete the total synthesis of xyloketal D.A second class of biocatalytic oxidation that we have employed in synthesis is the hydroxylative dearomatization of resorcinol compounds using flavin-dependent monooxygenases (FDMOs). We anticipated that the catalyst-controlled site- and stereoselectivity of FDMOs would enable the total synthesis of azaphilone natural products. Azaphilones are bioactive compounds characterized by a pyranoquinone bicyclic core and a fully substituted chiral carbon atom. We leveraged the stereodivergent reactivity of FDMOs AzaH and AfoD to achieve the enantioselective synthesis of trichoflectin enantiomers, deflectin 1a, and lunatoic acid. We also leveraged FDMOs to construct tropolone and sorbicillinoid natural products. Tropolones are a structurally diverse class of bioactive molecules characterized by an aromatic cycloheptatriene core bearing an α-hydroxyketone moiety. We developed a two-step biocatalytic cascade to the tropolone natural product stipitatic aldehyde using the FDMO TropB and a NHI monooxygenase TropC. The FDMO SorbC obtained from the sorbicillin biosynthetic pathway was used in the concise total synthesis of a urea sorbicillinoid natural product.Our long-standing interest in using enzymes to carry out C-H hydroxylation reactions has also been channeled for the late-stage diversification of complex scaffolds. For example, we have used Rieske oxygenases to hydroxylate the tricyclic core common to paralytic shellfish toxins. The systemic toxicity of these compounds can be reduced by adding hydroxyl and sulfate groups, which improves their properties and potential as therapeutic agents. The enzymes SxtT, GxtA, SxtN, and SxtSUL were used to carry out selective C-H hydroxylation and O-sulfation in saxitoxin and related structures. We conclude this Account with a discussion of existing challenges in biocatalysis and ways we can currently address them.

The Development of Biocatalysis as a Tool for Drug Discovery.

Enzymes are versatile biocatalysts capable of performing selective reactions. The advantages of enzymes in comparison to classical chemistry including chemical catalysts are the generally milder process conditions and avoidance of harmful reactants. Their high selectivity and specificity are especially beneficial for the enzymatic synthesis of new products with potential applications in drug research. Therefore, in the past decades, the utilization of isolated enzymes or whole-cell biocatalysts has spread through a growing number of biotechnological industries. The applications comprise the production of chiral building blocks for the pharmaceutical and fine chemical industry, the enzymatic synthesis of drug metabolites for testing of toxicity, function, biological activity, degradation and the production of biocatalytically modified natural products, which all play a role in drug discovery. Especially Oreste Ghisalba's contributions, which paved the way for the industrial use of enzymes, will be considered in this review.

Broadening the Scope of Biocatalysis in Sustainable Organic Synthesis.

This Review is aimed at synthetic organic chemists who may be familiar with organometallic catalysis but have no experience with biocatalysis, and seeks to provide an answer to the perennial question: if it is so attractive, why wasn't it extensively used in the past? The development of biocatalysis in industrial organic synthesis is traced from the middle of the last century. Advances in molecular biology in the last two decades, in particular genome sequencing, gene synthesis and directed evolution of proteins, have enabled remarkable improvements in scope and substantially reduced biocatalyst development times and cost contributions. Additionally, improvements in biocatalyst recovery and reuse have been facilitated by developments in enzyme immobilization technologies. Biocatalysis has become eminently competitive with chemocatalysis and the biocatalytic production of important pharmaceutical intermediates, such as enantiopure alcohols and amines, has become mainstream organic synthesis. The synthetic space of biocatalysis has significantly expanded and is currently being extended even further to include new-to-nature biocatalytic reactions.

Recent developments in biocatalysis in multiphasic ionic liquid reaction systems.

Ionic liquids are well known and frequently used 'designer solvents' for biocatalytic reactions. This review highlights recent achievements in the field of multiphasic ionic liquid-based reaction concepts. It covers classical biphasic systems including supported ionic liquid phases, thermo-regulated multi-component solvent systems (TMS) and polymerized ionic liquids. These powerful concepts combine unique reaction conditions with a high potential for future applications on a laboratory and industrial scale. The presence of a multiphasic system simplifies downstream processing due to the distribution of the catalyst and reactants in different phases.

Oxygen Activation and Radical Transformations in Heme Proteins and Metalloporphyrins.

As a result of the adaptation of life to an aerobic environment, nature has evolved a panoply of metalloproteins for oxidative metabolism and protection against reactive oxygen species. Despite the diverse structures and functions of these proteins, they share common mechanistic grounds. An open-shell transition metal like iron or copper is employed to interact with O2 and its derived intermediates such as hydrogen peroxide to afford a variety of metal–oxygen intermediates. These reactive intermediates, including metal-superoxo, -(hydro)peroxo, and high-valent metal–oxo species, are the basis for the various biological functions of O2-utilizing metalloproteins. Collectively, these processes are called oxygen activation. Much of our understanding of the reactivity of these reactive intermediates has come from the study of heme-containing proteins and related metalloporphyrin compounds. These studies not only have deepened our understanding of various functions of heme proteins, such as O2 storage and transport, degradation of reactive oxygen species, redox signaling, and biological oxygenation, etc., but also have driven the development of bioinorganic chemistry and biomimetic catalysis. In this review, we survey the range of O2 activation processes mediated by heme proteins and model compounds with a focus on recent progress in the characterization and reactivity of important iron–oxygen intermediates. Representative reactions initiated by these reactive intermediates as well as some context from prior decades will also be presented. We will discuss the fundamental mechanistic features of these transformations and delineate the underlying structural and electronic factors that contribute to the spectrum of reactivities that has been observed in nature as well as those that have been invented using these paradigms. Given the recent developments in biocatalysis for non-natural chemistries and the renaissance of radical chemistry in organic synthesis, we envision that new enzymatic and synthetic transformations will emerge based on the radical processes mediated by metalloproteins and their synthetic analogs.

8th International Congress on Biocatalysis (Biocat2016), Hamburg, Germany, 28 August–1 September, 2016

The “8th International Congress on Biocatalysis (biocat2016)” is part of a biennial conference series. Biocatalysis is a topic based on the edge of biology and chemistry, which brings together scientists from the life sciences, engineers and computer scientists. This international conference serves as a platform to meet researchers from all over the world, to find collaboration partners for future projects and to gain novel insights into modern topics and techniques. Biocat covers the most exciting aspects and the latest developments in biocatalysis, including enzyme discovery, evolution and application, bioprocess engineering, cascade reaction systems and nanobiotechnology. In 2016, we welcomed 367 expert delegates in the respective fields. Established and young scientists from academia and the industry presented 51 lectures, 37 lightning talks and 234 posters. In addition, the biocat award, which is among the most prestigious awards in the field of biotechnology, has been awarded for the sixth time in the categories “Science in academia”, “Lifetime achievement” and “Industry”.

An artificial self-sufficient cytochrome P450 directly nitrates fluorinated tryptophan analogs with a different regio-selectivity.

Aromatic nitration is an immensely important industrial process to produce chemicals for a variety of applications, but it often suffers from multiple unsolved challenges. Enzymes as biocatalysts have been increasingly used for organic chemistry synthesis due to their high selectivity and environmental friendliness, but nitration has benefited minimally from the development of biocatalysis. In this work, we aimed to develop TxtE as practical biocatalysts for aromatic nitration. TxtE is a unique class I cytochrome P450 enzyme that nitrates the indole of l-tryptophan. To develop cost-efficient nitration processes, we fused TxtE with the reductase domains of CYP102A1 (P450BM3) and of P450RhF to create class III self-sufficient biocatalysts. The best engineered fusion protein was comparable with wild type TxtE in terms of nitration performance and other key biochemical properties. To demonstrate the application potential of the fusion enzyme, we nitrated 4-F-dl-tryptophan and 5-F-l-tryptophan in large scale enzymatic reactions. Tandem MS/MS and NMR analyses of isolated products revealed altered nitration sites. To our knowledge, these studies represent the first practice in developing biological nitration approaches and lay a solid basis to the use of TxtE-based biocatalysts for the production of valuable nitroaromatics.

Recent developments in biocatalysis beyond the laboratory

Recent developments in biocatalysis, where implementation beyond the laboratory has been demonstrated, are explored: the use of transglutaminases to modify foods, reduce allergenicity and produce advanced materials, lipases for biodiesel production, and transaminases for biochemical production. The availability and application of enzymes at pilot and larger scale opens up possibilities for further improvements of biocatalyst-based processes and the development of new processes. Enzyme production, stability, activity, re-use, and product retrieval are common challenges for biocatalytic processes. We explore recent advances in biocatalysis within the process chain, such as protein engineering, enzyme expression, and biocatalyst immobilization, in the context of these challenges.

Biocatálisis y biotecnología

Biocatalysis has emerged as a rich field within Biotechnology, enabling the application of enzymes in a wide range of industries ranging from pharmaceuticals and fine chemicals to food and energy. This striking development of Biocatalysis is due to novel technologies such as bioinformatics, high-throughput screening (HTS), directed evolution, as well as other well-established techniques such as enzyme immobilization and protein engineering or medium engineering. Sustainable manufacturing is a major driver of Biocatalysis, which will provide many real challenges and opportunities for the future. In this article, some of the main methods in enzyme technology have been reviewed, as well as several biotechnological applications of enzymes in industry. Finally, a brief overview of the situation of Biocatalysis in both Spanish academia and industry has also been reported.

ChemInform Abstract: From Commercial Enzymes to Biocatalysts Designed by Protein Engineering

AbstractReview: ca. 50 refs.

From Commercial Enzymes to Biocatalysts Designed by Protein Engineering

This account provides a personal view on the development of biocatalysis over the last two decades. Examples include the use of commercial enzymes, such as lipases, (recombinant) esterases, transaminases, and Baeyer–Villiger monooxygenases for the synthesis of optically pure compounds. The opportunity provided by modern protein engineering methods to tailor design an enzyme for a given scientific problem (substrate scope, selectivity, stability) is emphasized together with concepts to boost this technology in terms of timelines and success. 1 Introduction 2 Unexpected Discoveries 2.1 To Protect and Serve 2.2 ‘Abnormal’ Access to β-Amino Acids 3 Defined Enzyme Is Better Than Crude Extract 4 New Horizons Opened by Protein Engineering 4.1 Random Mutagenesis Can Give Random Results 5 Exploring Sequence and Structure Databases 5.1 Massive Alignment Identifies Evolutionary Variations 5.2 Fixing Wrong Annotations Can Yield a Toolbox of Novel Enzymes 6 Conclusion

Interface Engineering Catalytic Graphene for Smart Colorimetric Biosensing

Herein a hybrid catalyst consisting of "naked" Au-NPs in situ grown on graphene sheets is engineered, which exhibits a synergetic effect in mimicking peroxidase at its interface, although free Au-NPs or graphene alone has very little activity. What is more, one of the unique features of our synergetic catalyst is that its interface can be reversibly switched from "inactive" to "active" upon treatment with different ssDNA species in solution, thus providing a powerful and versatile basis for designing graphene/DNA-based label-free colorimetric biosensors. Compared with other signal transduction modes in traditional graphene/aptamer-based systems, our novel signaling strategy not only avoids any labeling or modification procedures but also reduces the background signal due to the "off-on" switching mode during the sensing. Furthermore, this facile and general approach can be applicable to the other extended graphene/aptamer-based systems for colorimetric detection of a wide range of analytes. We envision that the tunable graphene-based smart interface could find potential applications in the development of biocatalysis, bioassays, and smart material devices in the future.

Strategies for discovery and improvement of enzyme function: state of the art and opportunities

SummaryDevelopments in biocatalysis have been largely fuelled by consumer demands for new products, industrial attempts to improving existing process and minimizing waste, coupled with governmental measures to regulate consumer safety along with scientific advancements. One of the major hurdles to application of biocatalysis to chemical synthesis is unavailability of the desired enzyme to catalyse the reaction to allow for a viable process development. Even when the desired enzyme is available it often forces the process engineers to alter process parameters due to inadequacies of the enzyme, such as instability, inhibition, low yield or selectivity, etc. Developments in the field of enzyme or reaction engineering have allowed access to means to achieve the ends, such as directed evolution, de novo protein design, use of non‐conventional media, using new substrates for old enzymes, active‐site imprinting, altering temperature, etc. Utilization of enzyme discovery and improvement tools therefore provides a feasible means to overcome this problem. Judicious employment of these tools has resulted in significant advancements that have leveraged the research from laboratory to market thus impacting economic growth; however, there are further opportunities that have not yet been explored. The present review attempts to highlight some of these achievements and potential opportunities.

ChemInform Abstract: Industrial Developments in Biocatalysis

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New Developments in Biocatalysis

New Developments in Biocatalysis

New Developments in Biocatalysis

Advanced Synthesis & CatalysisVolume 345, Issue 6-7 p. 651-651 CommentaryFree Access New Developments in Biocatalysis Chi-Huey Wong, Chi-Huey Wong wong@scripps.edu Ernest W. Hahn Professor and Chair, Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd., BCC 338 La Jolla, CA 92037, USA Phone: (+1)-858-784-2487, Fax: (+1)-858-784-2409, web: http://wong.scripps.edu/Search for more papers by this author Chi-Huey Wong, Chi-Huey Wong wong@scripps.edu Ernest W. Hahn Professor and Chair, Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd., BCC 338 La Jolla, CA 92037, USA Phone: (+1)-858-784-2487, Fax: (+1)-858-784-2409, web: http://wong.scripps.edu/Search for more papers by this author First published: 03 June 2003 https://doi.org/10.1002/adsc.200303062AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume345, Issue6-7Special Issue: Biocatalysis 2003June 2003Pages 651-651 RelatedInformation