Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 250
Filter
1.
Nat Catal ; 7(5): 585-592, 2024 May.
Article in English | MEDLINE | ID: mdl-39006156

ABSTRACT

Intermolecular functionalization of tertiary C-H bonds to construct fully substituted stereogenic carbon centers represents a formidable challenge: without the assistance of directing groups, state-of-the-art catalysts struggle to introduce chirality to racemic tertiary sp 3 -carbon centers. Direct asymmetric functionalization of such centers is a worthy reactivity and selectivity goal for modern biocatalysis. Here we present an engineered nitrene transferase (P411-TEA-5274), derived from a bacterial cytochrome P450, that is capable of aminating tertiary C-H bonds to provide chiral α-tertiary primary amines with high efficiency (up to 2300 total turnovers) and selectivity (up to >99% enantiomeric excess (e.e.)). The construction of fully substituted stereocenters with methyl and ethyl groups underscores the enzyme's remarkable selectivity. A comprehensive substrate scope study demonstrates the biocatalyst's compatibility with diverse functional groups and tertiary C-H bonds. Mechanistic studies elucidate how active-site residues distinguish between the enantiomers and enable the enzyme to perform this transformation with excellent enantioselectivity.

2.
J Am Chem Soc ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958264

ABSTRACT

Boronic acids and esters are highly regarded for their safety, unique reactivity, and versatility in synthesizing a wide range of small molecules, bioconjugates, and materials. They are not exploited in biocatalytic synthesis, however, because enzymes that can make, break, or modify carbon-boron bonds are rare. We wish to combine the advantages of boronic acids and esters for molecular assembly with biocatalysis, which offers the potential for unsurpassed selectivity and efficiency. Here, we introduce an engineered protoglobin nitrene transferase that catalyzes the new-to-nature amination of boronic acids using hydroxylamine. Initially targeting aryl boronic acids, we show that the engineered enzyme can produce a wide array of anilines with high yields and total turnover numbers (up to 99% yield and >4000 TTN), with water and boric acid as the only byproducts. We also demonstrate that the enzyme is effective with bench-stable boronic esters, which hydrolyze in situ to their corresponding boronic acids. Exploring the enzyme's capacity for enantioselective catalysis, we found that a racemic alkyl boronic ester affords an enantioenriched alkyl amine, a transformation not achieved with chemocatalysts. The formation of an exclusively unrearranged product during the amination of a boronic ester radical clock and the reaction's stereospecificity support a two-electron process akin to a 1,2-metallate shift mechanism. The developed transformation enables new biocatalytic routes for synthesizing chiral amines.

3.
Nat Chem Biol ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38744987

ABSTRACT

Aromatic amino acids and their derivatives are diverse primary and secondary metabolites with critical roles in protein synthesis, cell structure and integrity, defense and signaling. All de novo aromatic amino acid production relies on a set of ancient and highly conserved chemistries. Here we introduce a new enzymatic transformation for L-tyrosine synthesis by demonstrating that the ß-subunit of tryptophan synthase-which natively couples indole and L-serine to form L-tryptophan-can act as a latent 'tyrosine synthase'. A single substitution of a near-universally conserved catalytic residue unlocks activity toward simple phenol analogs and yields exclusive para carbon-carbon bond formation to furnish L-tyrosines. Structural and mechanistic studies show how a new active-site water molecule orients phenols for a nonnative mechanism of alkylation, with additional directed evolution resulting in a net >30,000-fold rate enhancement. This new biocatalyst can be used to efficiently prepare valuable L-tyrosine analogs at gram scales and provides the missing chemistry for a conceptually different pathway to L-tyrosine.

4.
BMJ Open ; 14(4): e078671, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594188

ABSTRACT

OBJECTIVES: Government guidance to manage COVID-19 was challenged by low levels of health and digital literacy and lack of information in different languages. 'Covid Confidence' sessions (CC-sessions) were evaluated to assess their effectiveness in counteracting misinformation and provide an alternative source of information about the pandemic. DESIGN: We worked with community anchor organisations to co-ordinate online CC-sessions serving three economically deprived, ethnically mixed, neighbourhoods. We conducted a qualitative, participatory process evaluation, in tandem with the CC-sessions to explore whether a popular opinion leader/local champion model of health promotion could mobilise pandemic responses. Group discussions were supplemented by final interviews to assess changes in community capacity to mobilise. SETTING: Sheffield, England, September 2020 to November 2021. PARTICIPANTS: Community leaders, workers and volunteers representing a variety of local organisations resulted in 314 attendances at CC-sessions. A group of local health experts helped organisations make sense of government information. RESULTS: CC-sessions fostered cross-organisational relationships, which enabled rapid community responses. Community champions successfully adapted information to different groups. Listening, identifying individual concerns and providing practical support enabled people to make informed decisions on managing exposure and getting vaccinated. Some people were unable to comply with self-isolation due to overcrowded housing and the need to work. Communities drew on existing resources and networks. CONCLUSIONS: CC-sessions promoted stronger links between community organisations which reduced mistrust of government information. In future, government efforts to manage pandemics should partner with communities to codesign and implement prevention and control measures.


Subject(s)
COVID-19 , Humans , COVID-19/prevention & control , Pandemics/prevention & control , Capacity Building , Health Promotion/methods , England
5.
ACS Cent Sci ; 10(2): 226-241, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38435522

ABSTRACT

Enzymes can be engineered at the level of their amino acid sequences to optimize key properties such as expression, stability, substrate range, and catalytic efficiency-or even to unlock new catalytic activities not found in nature. Because the search space of possible proteins is vast, enzyme engineering usually involves discovering an enzyme starting point that has some level of the desired activity followed by directed evolution to improve its "fitness" for a desired application. Recently, machine learning (ML) has emerged as a powerful tool to complement this empirical process. ML models can contribute to (1) starting point discovery by functional annotation of known protein sequences or generating novel protein sequences with desired functions and (2) navigating protein fitness landscapes for fitness optimization by learning mappings between protein sequences and their associated fitness values. In this Outlook, we explain how ML complements enzyme engineering and discuss its future potential to unlock improved engineering outcomes.

6.
J Am Chem Soc ; 146(2): 1580-1587, 2024 01 17.
Article in English | MEDLINE | ID: mdl-38166100

ABSTRACT

Lactones are cyclic esters with extensive applications in materials science, medicinal chemistry, and the food and perfume industries. Nature's strategy for the synthesis of many lactones found in natural products always relies on a single type of retrosynthetic strategy, a C-O bond disconnection. Here, we describe a set of laboratory-engineered enzymes that use a new-to-nature C-C bond-forming strategy to assemble diverse lactone structures. These engineered "carbene transferases" catalyze intramolecular carbene insertions into benzylic or allylic C-H bonds, which allow for the synthesis of lactones with different ring sizes and ring scaffolds from simple starting materials. Starting from a serine-ligated cytochrome P450 variant previously engineered for other carbene-transfer activities, directed evolution generated a variant P411-LAS-5247, which exhibits a high activity for constructing a five-membered ε-lactone, lactam, and cyclic ketone products (up to 5600 total turnovers (TTN) and >99% enantiomeric excess (ee)). Further engineering led to variants P411-LAS-5249 and P411-LAS-5264, which deliver six-membered δ-lactones and seven-membered ε-lactones, respectively, overcoming the thermodynamically unfavorable ring strain associated with these products compared to the γ-lactones. This new carbene-transfer activity was further extended to the synthesis of complex lactone scaffolds based on fused, bridged, and spiro rings. The enzymatic platform developed here complements natural biosynthetic strategies for lactone assembly and expands the structural diversity of lactones accessible through C-H functionalization.


Subject(s)
Cytochrome P-450 Enzyme System , Lactones , Lactones/chemistry , Catalysis , Cytochrome P-450 Enzyme System/chemistry , Methane
7.
J Am Chem Soc ; 146(5): 2959-2966, 2024 02 07.
Article in English | MEDLINE | ID: mdl-38270588

ABSTRACT

The mechanism of cyclopropanations with diazirines as air-stable and user-friendly alternatives to commonly employed diazo compounds within iron heme enzyme-catalyzed carbene transfer reactions has been studied by means of density functional theory (DFT) calculations of model systems, quantum mechanics/molecular mechanics (QM/MM) calculations, and molecular dynamics (MD) simulations of the iron carbene and the cyclopropanation transition state in the enzyme active site. The reaction is initiated by a direct diazirine-diazo isomerization occurring in the active site of the enzyme. In contrast, an isomerization mechanism proceeding via the formation of a free carbene intermediate in lieu of a direct, one-step isomerization process was observed for model systems. Subsequent reaction with benzyl acrylate takes place through stepwise C-C bond formation via a diradical intermediate, delivering the cyclopropane product. The origin of the observed diastereo- and enantioselectivity in the enzyme was investigated through MD simulations, which indicate a preferred formation of the cis-cyclopropane by steric control.


Subject(s)
Diazomethane , Heme , Methane/analogs & derivatives , Heme/chemistry , Models, Molecular , Iron , Cyclopropanes/chemistry , Catalysis
9.
Science ; 383(6681): 438-443, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38271505

ABSTRACT

Volatile methylsiloxanes (VMS) are man-made, nonbiodegradable chemicals produced at a megaton-per-year scale, which leads to concern over their potential for environmental persistence, long-range transport, and bioaccumulation. We used directed evolution to engineer a variant of bacterial cytochrome P450BM3 to break silicon-carbon bonds in linear and cyclic VMS. To accomplish silicon-carbon bond cleavage, the enzyme catalyzes two tandem oxidations of a siloxane methyl group, which is followed by putative [1,2]-Brook rearrangement and hydrolysis. Discovery of this so-called siloxane oxidase opens possibilities for the eventual biodegradation of VMS.

10.
Methods Enzymol ; 693: 1-30, 2023.
Article in English | MEDLINE | ID: mdl-37977727

ABSTRACT

Functionalizing inert C-H bonds selectively is a formidable task due to their strong bond energy and the difficulty of distinguishing chemically similar C-H bonds. While enzymatic oxygenation of C-H bonds is ubiquitous and well established, there is currently no known natural enzymatic process for direct nitrogen insertion. Instead, nature typically relies on pre-oxidized compounds for nitrogen incorporation. Direct biocatalytic C-H amination methods developed in the last few years are only selective for activated C-H bonds that contain specific groups such as benzylic, allylic, or propargylic groups. However, we recently used directed evolution to generate cytochrome P411 enzymes (engineered P450 enzymes with axial ligand mutation from cysteine to serine) that directly aminate inert C-H bonds with high site-, diastereo-, and enantioselectivity. Using these enzymes, we demonstrated the regiodivergent desymmetrization of methylcyclohexane, among other reactions. This chapter provides a comprehensive account of the experimental protocols used to evolve P411s for aminating unactivated C-H bonds. These methods are illustrative and can be adapted for other directed enzyme evolution campaigns.


Subject(s)
Cysteine , Cytochrome P-450 Enzyme System , Amination , Biocatalysis , Cytochrome P-450 Enzyme System/metabolism , Cysteine/metabolism , Nitrogen/chemistry
11.
Methods Enzymol ; 693: 375-403, 2023.
Article in English | MEDLINE | ID: mdl-37977737

ABSTRACT

Volatile methylsiloxanes (VMS) are a class of non-biodegradable anthropogenic compounds with propensity for long-range transport and potential for bioaccumulation in the environment. As a proof-of-principle for biological degradation of these compounds, we engineered P450 enzymes to oxidatively cleave Si-C bonds in linear and cyclic VMS. Enzymatic reactions with VMS are challenging to screen with conventional tools, however, due to their volatility, poor aqueous solubility, and tendency to extract polypropylene from standard 96-well deep-well plates. To address these challenges, we developed a new biocatalytic reactor consisting of individual 2-mL glass shells assembled in conventional 96-well plate format. In this chapter, we provide a detailed account of the assembly and use of the 96-well glass shell reactors for screening biocatalytic reactions. Additionally, we discuss the application of GC/MS analysis techniques for VMS oxidase reactions and modified procedures for validating improved variants. This protocol can be adopted broadly for biocatalytic reactions with substrates that are volatile or not suitable for polypropylene plates.


Subject(s)
Polypropylenes , Siloxanes , Siloxanes/analysis , Siloxanes/chemistry , Water/chemistry , Bioreactors , Glass
12.
J Am Chem Soc ; 145(37): 20196-20201, 2023 09 20.
Article in English | MEDLINE | ID: mdl-37671894

ABSTRACT

Hydroxylamine-derived reagents have enabled versatile nitrene transfer reactions for introducing nitrogen-containing functionalities in small-molecule catalysis, as well as biocatalysis. These reagents, however, result in a poor atom economy and stoichiometric organic waste. Activating hydroxylamine (NH2OH) for nitrene transfer offers a low-cost and sustainable route to amine synthesis, since water is the sole byproduct. Despite its presence in nature, hydroxylamine is not known to be used for enzymatic nitrogen incorporation in biosynthesis. Here, we report an engineered heme enzyme that can utilize hydroxylammonium chloride, an inexpensive commodity chemical, for nitrene transfer. Directed evolution of Pyrobaculum arsenaticum protoglobin generated efficient enzymes for benzylic C-H primary amination and styrene aminohydroxylation. Mechanistic studies supported a stepwise radical pathway involving rate-limiting hydrogen atom transfer. This unprecedented activity is a useful addition to the "nitrene transferase" repertoire and hints at possible future discovery of natural enzymes that use hydroxylamine for amination chemistry.


Subject(s)
Hydroxylamines , Nitrogen , Hydroxylamine , Amination
13.
J Am Chem Soc ; 145(29): 16176-16185, 2023 07 26.
Article in English | MEDLINE | ID: mdl-37433085

ABSTRACT

In nature and synthetic chemistry, stereoselective [2 + 1] cyclopropanation is the most prevalent strategy for the synthesis of chiral cyclopropanes, a class of key pharmacophores in pharmaceuticals and bioactive natural products. One of the most extensively studied reactions in the organic chemist's arsenal, stereoselective [2 + 1] cyclopropanation, largely relies on the use of stereodefined olefins, which can require elaborate laboratory synthesis or tedious separation to ensure high stereoselectivity. Here, we report engineered hemoproteins derived from a bacterial cytochrome P450 that catalyze the synthesis of chiral 1,2,3-polysubstituted cyclopropanes, regardless of the stereopurity of the olefin substrates used. Cytochrome P450BM3 variant P411-INC-5185 exclusively converts (Z)-enol acetates to enantio- and diastereoenriched cyclopropanes and in the model reaction delivers a leftover (E)-enol acetate with 98% stereopurity, using whole Escherichia coli cells. P411-INC-5185 was further engineered with a single mutation to enable the biotransformation of (E)-enol acetates to α-branched ketones with high levels of enantioselectivity while simultaneously catalyzing the cyclopropanation of (Z)-enol acetates with excellent activities and selectivities. We conducted docking studies and molecular dynamics simulations to understand how active-site residues distinguish between the substrate isomers and enable the enzyme to perform these distinct transformations with such high selectivities. Computational studies suggest the observed enantio- and diastereoselectivities are achieved through a stepwise pathway. These biotransformations streamline the synthesis of chiral 1,2,3-polysubstituted cyclopropanes from readily available mixtures of (Z/E)-olefins, adding a new dimension to classical cyclopropanation methods.


Subject(s)
Cyclopropanes , Cytochrome P-450 Enzyme System , Cyclopropanes/chemistry , Stereoisomerism , Cytochrome P-450 Enzyme System/metabolism , Alcohols , Acetates , Alkenes/chemistry
14.
ACS Synth Biol ; 12(8): 2444-2454, 2023 08 18.
Article in English | MEDLINE | ID: mdl-37524064

ABSTRACT

With advances in machine learning (ML)-assisted protein engineering, models based on data, biophysics, and natural evolution are being used to propose informed libraries of protein variants to explore. Synthesizing these libraries for experimental screens is a major bottleneck, as the cost of obtaining large numbers of exact gene sequences is often prohibitive. Degenerate codon (DC) libraries are a cost-effective alternative for generating combinatorial mutagenesis libraries where mutations are targeted to a handful of amino acid sites. However, existing computational methods to optimize DC libraries to include desired protein variants are not well suited to design libraries for ML-assisted protein engineering. To address these drawbacks, we present DEgenerate Codon Optimization for Informed Libraries (DeCOIL), a generalized method that directly optimizes DC libraries to be useful for protein engineering: to sample protein variants that are likely to have both high fitness and high diversity in the sequence search space. Using computational simulations and wet-lab experiments, we demonstrate that DeCOIL is effective across two specific case studies, with the potential to be applied to many other use cases. DeCOIL offers several advantages over existing methods, as it is direct, easy to use, generalizable, and scalable. With accompanying software (https://github.com/jsunn-y/DeCOIL), DeCOIL can be readily implemented to generate desired informed libraries.


Subject(s)
Protein Engineering , Software , Gene Library , Machine Learning , Codon/genetics
15.
Angew Chem Int Ed Engl ; 62(35): e202303879, 2023 08 28.
Article in English | MEDLINE | ID: mdl-37260412

ABSTRACT

We report a computationally driven approach to access enantiodivergent enzymatic carbene N-H insertions catalyzed by P411 enzymes. Computational modeling was employed to rationally guide engineering efforts to control the accessible conformations of a key lactone-carbene (LAC) intermediate in the enzyme active site by installing a new H-bond anchoring point. This H-bonding interaction controls the relative orientation of the reactive carbene intermediate, orienting it for an enantioselective N-nucleophilic attack by the amine substrate. By combining MD simulations and site-saturation mutagenesis and screening targeted to only two key residues, we were able to reverse the stereoselectivity of previously engineered S-selective P411 enzymes. The resulting variant, L5_FL-B3, accepts a broad scope of amine substrates for N-H insertion with excellent yields (up to >99 %), high efficiency (up to 12 300 TTN), and good enantiocontrol (up to 7 : 93 er).


Subject(s)
Methane , Protein Engineering , Methane/chemistry , Catalytic Domain , Amines
16.
Res Sq ; 2023 Apr 12.
Article in English | MEDLINE | ID: mdl-37090661

ABSTRACT

In nature and synthetic chemistry, stereoselective [2+1] cyclopropanation is the most prevalent strategy for the synthesis of chiral cyclopropanes, a class of key pharmacophores in pharmaceuticals and bioactive natural products. One of the most extensively studied reactions in the organic chemist's arsenal, stereoselective [2+1] cyclopropanation, largely relies on the use of stereodefined olefins, which require elaborate laboratory synthesis or tedious separation to ensure high stereoselectivity. Here we report engineered hemoproteins derived from a bacterial cytochrome P450 that catalyze the synthesis of chiral 1,2,3-polysubstituted cyclopropanes, regardless of the stereopurity of the olefin substrates used. Cytochrome P450 BM3 variant IC-G3 exclusively converts ( Z )-enol acetates to enantio- and diastereoenriched cyclopropanes and in our model reaction delivers a leftover ( E )-enol acetate with 98% stereopurity, using whole Escherichia coli cells. IC-G3 was further engineered with a single mutation to enable the biotransformation of ( E )-enol acetates to α -branched ketones with high levels of enantioselectivity while simultaneously catalyzing the cyclopropanation of ( Z )-enol acetates with excellent activities and selectivities. We conducted docking studies and molecular dynamics simulations to understand how active-site residues distinguish between the substrate isomers and enable the enzyme to perform these distinct transformations with such high selectivities. Computational studies suggest the observed enantio- and diastereoselectivities are achieved through a stepwise pathway. These biotransformations streamline the synthesis of chiral 1,2,3-polysubstituted cyclopropanes from readily available mixtures of ( Z/E )-olefins, adding a new dimension to classical cyclopropanation methods.

17.
Nat Catal ; 6(2): 152-160, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36875868

ABSTRACT

The ubiquity of C-H bonds presents an attractive opportunity to elaborate and build complexity in organic molecules. Methods for selective functionalization, however, often must differentiate among multiple chemically similar and, in some cases indistinguishable, C-H bonds. An advantage of enzymes is that they can be finely tuned using directed evolution to achieve control over divergent C-H functionalization pathways. Here, we demonstrate engineered enzymes that effect a new-to-nature C-H alkylation with unparalleled selectivity: two complementary carbene C-H transferases derived from a cytochrome P450 from Bacillus megaterium deliver an α-cyanocarbene into the α-amino C(sp3)-H bonds or the ortho-arene C(sp2)-H bonds of N-substituted arenes. These two transformations proceed via different mechanisms, yet only minimal changes to the protein scaffold (nine mutations, less than 2% of the sequence) were needed to adjust the enzyme's control over the site-selectivity of cyanomethylation. The X-ray crystal structure of the selective C(sp3)-H alkylase, P411-PFA, reveals an unprecedented helical disruption which alters the shape and electrostatics in the enzyme active site. Overall, this work demonstrates the advantages of enzymes as C-H functionalization catalysts for divergent molecular derivatization.

18.
J Am Chem Soc ; 145(13): 7159-7165, 2023 04 05.
Article in English | MEDLINE | ID: mdl-36948184

ABSTRACT

Microcrystal electron diffraction (MicroED) is an emerging technique that has shown great potential for describing new chemical and biological molecular structures. Several important structures of small molecules, natural products, and peptides have been determined using ab initio methods. However, only a couple of novel protein structures have thus far been derived by MicroED. Taking advantage of recent technological advances, including higher acceleration voltage and using a low-noise detector in counting mode, we have determined the first structure of an Aeropyrum pernix protoglobin (ApePgb) variant by MicroED using an AlphaFold2 model for phasing. The structure revealed that mutations introduced during directed evolution enhance carbene transfer activity by reorienting an α helix of ApePgb into a dynamic loop, making the catalytic active site more readily accessible. After exposing the tiny crystals to the substrate, we also trapped the reactive iron-carbenoid intermediate involved in this engineered ApePgb's new-to-nature activity, a challenging carbene transfer from a diazirine via a putative metallo-carbene. The bound structure discloses how an enlarged active site pocket stabilizes the carbene bound to the heme iron and, presumably, the transition state for the formation of this key intermediate. This work demonstrates that improved MicroED technology and the advancement in protein structure prediction now enable investigation of structures that was previously beyond reach.


Subject(s)
Electrons , Proteins , Proteins/chemistry , Peptides , Methane
19.
Angew Chem Int Ed Engl ; 62(4): e202208936, 2023 01 23.
Article in English | MEDLINE | ID: mdl-36533936

ABSTRACT

Trifluoromethyl-substituted cyclopropanes (CF3 -CPAs) constitute an important class of compounds for drug discovery. While several methods have been developed for synthesis of trans-CF3 -CPAs, stereoselective production of corresponding cis-diastereomers remains a formidable challenge. We report a biocatalyst for diastereo- and enantio-selective synthesis of cis-CF3 -CPAs with activity on a variety of alkenes. We found that an engineered protoglobin from Aeropyrnum pernix (ApePgb) can catalyze this unusual reaction at preparative scale with low-to-excellent yield (6-55 %) and enantioselectivity (17-99 % ee), depending on the substrate. Computational studies revealed that the steric environment in the active site of the protoglobin forced iron-carbenoid and substrates to adopt a pro-cis near-attack conformation. This work demonstrates the capability of enzyme catalysts to tackle challenging chemistry problems and provides a powerful means to expand the structural diversity of CF3 -CPAs for drug discovery.


Subject(s)
Cyclopropanes , Methane , Cyclopropanes/chemistry , Stereoisomerism , Methane/chemistry , Catalysis
20.
ACS Cent Sci ; 9(12): 2333-2338, 2023 Dec 27.
Article in English | MEDLINE | ID: mdl-38161360

ABSTRACT

Nature harnesses exquisite enzymatic cascades to construct N-heterocycles and further uses these building blocks to assemble the molecules of life. Here we report an enzymatic platform to construct important chiral N-heterocyclic products, pyrrolidines and indolines, via abiological intramolecular C(sp3)-H amination of organic azides. Directed evolution of cytochrome P411 (a P450 enzyme with serine as the heme-ligating residue) yielded variant P411-PYS-5149, capable of catalyzing the insertion of alkyl nitrene into C(sp3)-H bonds to build pyrrolidine derivatives with good enantioselectivity and catalytic efficiency. Further evolution of activity on aryl azide substrates yielded variant P411-INS-5151 that catalyzes intramolecular C(sp3)-H amination to afford chiral indolines. In addition, we show that these enzymatic aminations can be coupled with a P411-based carbene transferase or a tryptophan synthase to generate an α-amino lactone or a noncanonical amino acid, respectively, underscoring the power of new-to-nature biocatalysis in complexity-building chemical synthesis.

SELECTION OF CITATIONS
SEARCH DETAIL
...