Recommended Free Tools
Engineered cytochrome P450 enzymes have been shown to perform an atom-transfer radical cyclization (ATRC) that no known natural enzyme performs. In the 2021 Science study by Qi Zhou, Michael Chin, Yue Fu, Peng Liu and Yang Yang, evolved P450 variants converted bromoalkene amides into lactams, with reported maxima of up to 97% enantioselectivity and up to 96% diastereoselectivity. Those figures are best results for particular substrates, not guarantees for every reaction, and the work remains a research demonstration rather than evidence of industrial deployment.
What the engineered enzymes actually do
Cytochrome P450s are heme-containing metalloenzymes best known for selective oxidation. In biology, they insert oxygen into molecules, often at a defined position and with control over three-dimensional arrangement. Zhou and colleagues repurposed that protein framework for a different reaction class: atom-transfer radical cyclization.
As an Amazon Associate I earn from qualifying purchases.
The starting molecules contain three key features in one amide substrate: a bromide that can participate in atom transfer, an alkene that can accept a radical, and an amide framework that becomes part of the product. The engineered enzyme guides the substrate through a radical cyclization and produces a lactam, a cyclic amide. The transformation is therefore not a normal P450 reaction that happens to have a new substrate; it is a deliberately evolved catalytic function outside the enzyme’s natural chemistry.
The Tool Desk
Outbyte PC Repair FREEClear out junk files and repair common Windows errorsFree Scan →Outbyte Driver Updater FREEScan for outdated or missing drivers - takes under a minuteDriver Scan →The paper is “Stereodivergent atom-transfer radical cyclization by engineered cytochromes P450,” by Qi Zhou, Michael Chin, Yue Fu, Peng Liu and Yang Yang, published in Science 374 (2021), pages 1612–1616, DOI 10.1126/science.abk1603. An accessible 2022 report in Chemistry World describes the reported selectivity and gram-scale demonstrations. The publisher’s full article was not accessible for this account, so substrate-by-substrate values should not be inferred from the headline percentages.
#1 Best Overall
- FOR BASIC TEACHING TO ADVANCED SCIENCE: 444 pieces molecular model kit, including 136 atoms, 158 bonds and 150 parts for Carbon-60(Fullerene), provides to students from Grade 7 to Graduate level.
- TWO CHEMICAL STRUCTURE MODELS: The ball-and-stick models use spheres to represent atoms and sticks to represent chemical bonds. In the space-filling model, the spheres are drawn to scale and are next to one another as atoms are in real molecules.
- CHEMISTRY EDUCATIONAL MOLECULE MODEL IN 3D: It can display chemical structure, molecular bond, and bond angle in all directions. Demonstrate fundamental molecular geometry, chemical molecular structure, stereochemistry with 3D modeling studies.
- EASY TO LEARN: The universal standard adopted for each atom's color makes it easier for you to use and learn. Atoms and chemical bonds combine tightly and firmly and can be easily disassembled by disconnecting tools.
- If you’re not in love with it for whatever reason, we’ll give you a full replacement or refund—no questions asked. If you have any doubt, please tell us. With nothing to worry about, or even to share with your friends, try it now.
Why radical cyclization is difficult to control
Radical reactions are useful because they can form carbon–carbon bonds through highly reactive intermediates. That reactivity is also the central control problem. A freely diffusing radical can react through several pathways, and a cyclization can create one or more stereocenters. Conventional radical chemistry often needs carefully tuned reagents, solvents, temperatures and chiral catalysts to favor one product over another.
An enzyme offers a different control strategy. Its active site creates a confined environment in which the substrate is held in a particular orientation. Nearby amino-acid residues, the heme cofactor and the protein’s shape can influence which bond forms and which face of an alkene is attacked. Directed evolution changes those features through repeated mutation and screening rather than requiring a complete mechanistic design from first principles.
Atom transfer in this reaction
In ATRC, a halogen-bearing substrate participates in a sequence that generates a carbon-centered radical and then closes a ring by intramolecular addition to an alkene. The bromide is part of the radical-generation and atom-transfer logic; the alkene supplies the second reaction site. After cyclization, the molecule is converted into the lactam framework. The exact elementary steps and their relative rates depend on the substrate and enzyme variant, so the broad description should not be read as a claim that every substrate follows an identical pathway.
Two kinds of selectivity matter
- Enantioselectivity describes preference for one enantiomer, the pair of mirror-image products. It is commonly reported as an enantiomeric excess or a closely related percentage.
- Diastereoselectivity describes preference among products that are not mirror images, such as configurations at multiple newly formed stereocenters.
A reaction can be highly selective in one dimension and less selective in the other. Reporting both values is important because a useful lactam synthesis may require control over the absolute configuration and the relative configuration at the same time.
Rank #2
- Visualize Molecular: The molecular model kit simplifies complex chemistry concepts into tangible 3D structures improve learning efficiency, suitable for students from Grade 7 to Graduate level.
- 444 Pcs Complete Set: The atom model kit includes with 136 atoms,158 bonds, and 150 fullerene model parts, explore most the molecules structures from simple compounds to complex polymers.
- Effortless Assembly: Embedded component design ensures easy to construct Ball-and-stick and Space-filling models that maximizes focus on exploration without complex assembly.
- Durable & Portable: Built to last, the chemistry set is crafted from high-quality materials. Plus, its portable Snap-Lock design allows you to take your experiments learning anywhere, between the home, classroom and lab.
- Essential Study Tool: Whether you're studying organic chemistry, biochemistry, or molecular biology, molecule building kit is an perfect learning tool for you deeper comprehension of molecular science.
How the researchers created the new activity
The project followed a practical enzyme-engineering workflow rather than assuming that a natural P450 would already catalyze ATRC.
- Screen metalloenzymes for a starting signal. The team examined metalloproteins for any activity in the target radical cyclization. A weak or imperfect signal can be enough to identify a scaffold that can be improved.
- Choose promising cytochrome P450 scaffolds. P450s already provide a well-developed protein environment around a heme metal. Their normal oxidation chemistry made them plausible candidates for controlling a reactive intermediate even though ATRC is not a known natural function.
- Apply directed evolution. The researchers introduced mutations, tested the resulting variants and retained versions with better activity or stereochemical control. Repeating this cycle tunes the protein’s pocket and the positioning of residues around the substrate.
- Build stereodivergent variants. The work produced evolved enzymes that favor different stereochemical outcomes. This is the meaning of “stereodivergent” in the paper’s title: protein variants can direct the same general transformation toward different configurations rather than merely making one product more efficiently.
- Demonstrate the chemistry in intact Escherichia coli. Whole cells containing the evolved enzymes were used for substrate demonstrations. The cell provides the biological context in which the enzyme is expressed and operated, while the substrate is converted to the lactam.
- Test a broader substrate set and increase the amount. The accessible report describes a wide substrate range and gram-scale demonstrations, showing that the result was not limited to a single analytical-scale vial.
This sequence illustrates what directed evolution contributes. It does not make an enzyme omnipotent; it searches a large sequence space for variants whose active sites happen to align the substrate and reactive intermediates more effectively.
What was reported, and how to interpret the numbers
| Reported feature | What the evidence supports | Important qualification |
|---|---|---|
| Reaction class | Atom-transfer radical cyclization catalyzed by engineered cytochrome P450s | The ATRC activity is described as new-to-nature; it is not a normal P450 function. |
| Product | Lactams formed from amide substrates bearing bromide and alkene groups | The accessible summary does not provide a complete substrate-by-substrate product table. |
| Enantioselectivity | Up to 97% | This is a maximum reported across the substrate set, not an average or universal value. |
| Diastereoselectivity | Up to 96% | This is also a maximum for particular examples; the value can differ between substrates and variants. |
| Scale | Gram-scale demonstrations were reported | Gram scale is an experimental demonstration, not proof of manufacturing robustness or commercial economics. |
| Biological format | Intact E. coli containing evolved enzymes | The report does not establish that the same performance transfers unchanged to a purified-enzyme or industrial process. |
The phrase “up to” carries most of the meaning in the two headline percentages. It identifies the best observed examples, not the performance a chemist should expect for an arbitrary bromoalkene amide. The available summary says the team covered a wide substrate range, but it does not expose enough substrate-level data to rank every variant or predict which lactam will reach either maximum.
Free tools Windows power users keep installed
One-click scans. No signup required.
What stereodivergence lets a synthetic chemist choose
Ordinary enzyme engineering often aims at one preferred stereoisomer. Here, the useful idea is a panel of variants with different preferences. If a target molecule requires the opposite configuration from the first enzyme tested, a different evolved catalyst may provide a direct route instead of forcing a separate inversion or resolution step.
Rank #3
- UNLOCK YOUR CHEMISTRY POTENTIAL: Our comprehensive molecular model kit includes 238 pieces, featuring 84 atoms, 153 bonds and a remover tool. Suitable for chemistry learners from beginners to advanced levels. Manufacturer recommended age: 15 years and up
- ORGANIZED STORAGE AND EASY LOCATING: Experience hassle-free organization with our storage box, complete with divided compartments and labeled sections. Say goodbye to clutter and quickly find the components you need
- EXTRA LEARNING MATERIALS FOR EXCELLENCE: Enhance your studies with our bonus 6-page learning guide and stencils. From grade 9 to college, from organic to inorganic, finish and master your assignments faster and create numerous molecular structures with ease
- IMMERSIVE 3D VISUAL LEARNING: Explore chemistry in a captivating way with our 3D visual learning approach. The universal color-coded Atomic Balls provide a better understanding of molecular structure, boosting your chemistry knowledge. It's also a perfect gift for someone who are going to learn those complex molecule
- EASY-TO-USE DESIGN: Crafted from smooth, burr-free plastic, our molecular science kit ensures easy assembly. With the included remover tool, disassembling is a breeze
The relevant comparison is not simply “which enzyme is most selective?” A practical choice depends on four linked questions:
- Which stereoisomer or relative configuration does the variant favor?
- Does the substrate fit the enzyme’s active site well enough to cyclize?
- What enantioselectivity and diastereoselectivity does that specific substrate achieve?
- Was the result shown only as an analytical experiment, or was a gram-scale run reported?
The accessible account does not provide a complete variant-by-variant matrix for those questions. It would therefore be misleading to assign a universal ranking or claim that one named variant is best for all substrates.
Why using whole cells matters
Running the reaction in intact E. coli can simplify handling of a fragile enzyme and its cofactors. The cell expresses the engineered protein and maintains the biochemical environment needed for the catalyst. That format can avoid an additional purification step during early development and allows researchers to test whether the enzyme functions in a realistic biological host.
Do these 3 things before closing this tab:
1Clear out junk files and repair common Windows errors2Fix the driver behind crashes, sound loss and screen glitches3Repair Windows errors before they cause bigger problemsWhole-cell operation also introduces variables that a purified-enzyme experiment might not share: substrate uptake, transport across membranes, competing metabolism, cell growth state and product toxicity. The reported demonstrations establish that the evolved P450s worked in the chosen cellular format; they do not, by themselves, establish long-term stability, space–time yield, recovery, waste treatment or regulatory suitability.
Rank #4
- ADVANCED LEARNING SCIENCE EDUCATION KIT --- Perfect chemistry model kit for modeling simple and small to more advanced and complex chemical structures for schools and college level, students of all ages, researchers and enthusiasts. Fun and interactive early learning molecular set for kids of all years and for use in the classroom.
- HIGH QUALITY --- Made from high quality durable materials designed for easy construction and perfect fit. These Molecular Model Kit pieces are color coded to national standards for easy ID. Organic Chemistry Model Kit includes box for easy storage and transport with your other textbooks, notes, and books. Excellent for the classroom.
- POWERFUL FUNCTIONS --- This Molecular Model Kit has a total of 136 pieces including short link remover tool. Super easy to build models for organic and inorganic chemistry, This model contains C, H, O, N, S and a variety of single and double bonds, Can be put high school, university chemistry in most of the organic or inorganic molecular structure model for the study of experimental operation.
- QUICK AND EASY ASSEMBLY OF COMPLEX STRUCTURES --- Atoms and bonds that are perfectly suited to being connected and disconnected easily without making your fingers hurt. We've also included a link remover to make the task of easy.
- CONVENIENT STORAGE --- The pieces come in a slim plastic box for convenient storage. See the pictures on this listing for a full understanding of what's inside
What this result changes in biocatalysis
It expands the definition of an enzyme reaction
Enzymes are often presented as catalysts for the transformations found in living organisms. This study shows a more flexible model: a natural protein scaffold can be remodeled to perform chemistry absent from known biology. The important unit is not “the enzyme’s original reaction,” but the combination of a metal center, a tunable protein pocket and an evolution-and-screening strategy.
It combines radical reactivity with biological selectivity
Radical intermediates are traditionally associated with broad, difficult-to-control reactivity. The engineered P450 approach places that reactivity inside a chiral protein environment. The reported selectivity demonstrates that radical bond construction and high stereocontrol are not mutually exclusive, at least for the tested lactam-forming substrates.
It offers a route to chiral lactam building blocks
Lactams are common structural elements in medicinal chemistry and in the synthesis of other nitrogen-containing molecules. A method that forms them while setting stereocenters can reduce the need for later separation or correction. The study establishes the synthetic concept; it does not establish a specific drug process or a commercial product.
Limits that a reader should keep in view
- Best-case statistics are not a guarantee. The 97% and 96% figures are maxima from selected examples.
- Substrate scope remains a practical question. A “wide” range does not mean every bromoalkene amide works, and the accessible report does not list complete performance for each substrate.
- Gram scale is not industrial scale. Larger production requires evidence about enzyme lifetime, mixing, oxygen or cofactor management, isolation, reproducibility and cost.
- New-to-nature does not mean fully understood. The engineered catalyst’s behavior is the result of protein sequence, substrate structure and reaction conditions; changing any of these can alter activity and selectivity.
- Commercial readiness was not demonstrated. The available sources provide no validated manufacturing economics, process robustness, pharmaceutical application or market availability.
- The primary article’s full details matter for replication. Without the complete experimental tables, it is not possible to state exact concentrations, reaction times, variant sequences or substrate-specific yields responsibly.
How to read future claims about engineered radical enzymes
When a later paper or supplier claims similar performance, check whether it reports the same distinctions used here. Look for the exact substrate, isolated yield, enantiomeric and diastereomeric analysis, enzyme format, reaction scale and number of repeated runs. “Up to” should be attached to a defined example, and a scale claim should state whether it means milligrams, grams or a process campaign.
Best Value
- Visualize Molecular: The molecular model kit simplifies complex chemistry concepts into tangible 3D structures improve learning efficiency, suitable for students from Grade 7 to Graduate level.
- 240 Pcs Complete Set: The atom model kit includes with 86 atoms and 154 bonds, explore most the molecules structures from simple compounds to complex polymers.
- Effortless Assembly: Embedded component design ensures easy to construct Ball-and-stick and Space-filling models that maximizes focus on exploration without complex assembly.
- Durable & Portable: Built to last, the chemistry set is crafted from high-quality materials. Plus, its portable design allows you to take your experiments learning anywhere, between the home, classroom and lab.
- Essential Study Tool: Whether you're studying organic chemistry, biochemistry, or molecular biology, molecule building kit is an perfect learning tool for you deeper comprehension of molecular science.
Also ask whether the catalyst is genuinely performing a new reaction or merely accelerating a transformation already known for that enzyme family. The significance of the Zhou study lies in the combination of a P450 scaffold, ATRC mechanism and engineered stereocontrol—not in the generic fact that a protein was used as a catalyst.
The broader lesson
Directed evolution can turn a protein’s latent physical properties into a reaction function that biology never selected. In this case, cytochrome P450s were redirected from their familiar stereoselective oxidations to an asymmetric radical cyclization that makes lactams from bromide- and alkene-containing amides. The strongest evidence is the reported stereocontrol—up to 97% enantioselectivity and up to 96% diastereoselectivity in individual examples—together with demonstrations on gram scale in engineered-cell systems.
That is a significant proof of principle, not a finished manufacturing technology. The next decisions for anyone trying to use the chemistry are substrate-specific: identify the required stereoisomer, test the available evolved variants, measure both selectivities for that exact substrate and then establish whether the whole-cell process is stable and scalable.
Quick Recap
Product prices and availability are accurate as of the date/time indicated and are subject to change. Any price and availability information displayed on Amazon at the time of purchase will apply.
