Their SMART method accelerates enzyme evolution by reducing the selection period for superior variants from several weeks to a few days, and decreases overall enzyme engineering campaign costs by eliminating the need for specialized equipment.

Enzymes are proteins that catalyze chemical reactions in living organisms. They are widely applied in industries such as food production, detergents, pharmaceuticals, and chemicals. However, for commercial use, natural enzymes often need improved stability, substrate specificity, or catalytic efficiency.

Directed evolution is a Nobel Prize-winning strategy for improving proteins. It introduces artificial mutations into their genes and then selects superior variants. This approach mimics natural evolution over several weeks instead of millions of years.

A significant challenge of this approach is that artificially induced mutations can generate up to 100 trillion candidate variants, which renders the screening process extremely time-consuming and expensive.

To address this challenge, researchers at ºÚÁϳԹÏÍø and their colleagues have developed SMART (Single-Molecule Assay on Ribonucleic acid by Translated product), an in vitro selection platform.

Their study demonstrated that SMART identifies improved enzyme variants much more rapidly and cost-effectively than conventional methods. The findings were published in the journal .

The SMART system was developed by a research group led by Associate Professor and Professor of the , in collaboration with researchers from the Institute of Science Tokyo and Saitama University. This approach successfully combines mRNA display, next-generation sequencing, and bioinformatics.

Key features of the SMART system

Typically, proteins and genes are physically separate, making it difficult and time-consuming to identify which gene encodes a discovered enzyme.

In the SMART system, puromycin acts as a chemical bridge, linking the enzyme protein to its corresponding blueprint, messenger RNA (mRNA). This mRNA display technique enables precise tracking of the relationship between individual proteins and their encoding genes at the single-molecule level.

Nakano emphasized, “In principle, there is no method for enzyme screening that is more efficient than this system. Screening enzymes at the single-molecule level has rarely been attempted before.”

SMART also incorporates an auxiliary unit for detecting enzyme activity. This study used engineered ascorbate peroxidase 2 (APEX2) as the auxiliary enzyme for oxidase screening. When the target oxidase is active and releases hydrogen peroxide (H?O?), APEX2 attaches a biotin marker to nearby molecules, enabling their isolation and capture.

Enzyme screening experiments using SMART

The researchers chose a yeast oxidase, SpDAAO, as a model enzyme because it has great potential for drug synthesis and diagnostics. The selection prioritized D-amino acids as enzyme substrates due to their growing relevance in medical applications.

The SMART method consists of several steps¡ªcreating a DNA library of enzyme variants, synthesizing enzymes in vitro, forming an mRNA display library, labeling catalytically active enzymes, isolating them with magnetic beads, and using sequencing data to guide subsequent rounds.

To assess the method, the team tested it on a simulated library with different ratios of active and inactive variants. After a single selection round, active variants were highly enriched, confirming SMART’s effectiveness.

In practical experiments, the team generated a mutant library by substituting the essential 232nd amino acid with each of the 20 other amino acids. Next-generation sequencing analysis showed that the wild-type (original form) Y232 was clearly selected (p < 0.001), reinforcing the method’s selectivity.

Initially, genetic analysis indicated selection of several variants, in addition to the original form. However, further statistical analysis identified these as experimental noise with minimal practical significance, supporting the method’s specificity.

Conclusion and future perspectives

The experiments showed that SMART selection is highly effective. At the same time, the team recognized the need for rigorous statistical analysis and careful experimentation, rather than relying solely on initial results.

The researchers expect SMART to be applicable beyond oxidases. They aim to facilitate the integration of novel enzymes into industry, establishing the system as a foundation for future enzyme development and practical biocatalytic solutions.

Publication

Kalhari Munaweera, Nana Odake, Hannah Patricia Halim, Kakeru Ikeda, Bo Zhu, Maurizio Camagna, Tomokazu Ito, Tetsuya Kitaguchi, Naoto Nemoto, Hideo Nakano, and Jasmina Damnjanovi? (2026). Harnessing the Power of SMART Single-Molecule Display for Enzyme Evolution: A Focus on Oxidase, ACS Synthetic Biology. DOI:

Funding

This work was supported by Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Early-Career scientists [grant number JP18K14387 and JP22K14828] and Grant-in-Aid for Transformative Research Areas (A) (Publicly Offered Research) [grant number JP25H02263], the Collaborative Research Program by Network Joint Research Center for Materials and Devices (Ministry of Education, Culture, Sports, Science and Technology -Japan: MEXT), and Retention, Development, and Promotion Program Program Aiming at Maximizing the Career Potential of Female Researchers, ºÚÁϳԹÏÍø, (MEXT’s Initiative for Realizing Diversity in the Research Environment, Leadership training type for women) awarded to Jasmina Damnjanovi?, and in part by Pre-Research Unit System of the Institute of Integrated Research, Institute of Science Tokyo and JSPS Grant-in-Aid for Transformative Research Areas (A) (Publicly Offered Research) [grant number JP24H01123] awarded to Bo Zhu.

Expert contact

Jasmina Damnjanovi?
Graduate School of Bioagricultural Sciences, ºÚÁϳԹÏÍø
Email: jasmina@agr.nagoya-u.ac.jp

Media contact

Naomi Inoue
International Communications Office, ºÚÁϳԹÏÍø
Email: icomm_research@t.mail.nagoya-u.ac.jp

Top image

The SMART single-molecule display model, predicted by Alphafold3, shows SpDAAO (red) linked to a puromycin linker (magenta) through puromycin incorporation into the growing polypeptide. The mRNA (gray) is hybridized and chemically joined to the linker, connecting it to its protein, SpDAAO. An auxiliary unit is added using ORC hairpin DNA (blue) with APEX2-scCro fusion protein (green).
Credit: Hideo Nakano and Jasmina Damnjanovi?

Scientists applied advanced mirror-making technology, originally developed for synchrotron radiation research at a Japanese X-ray facility, to build high-resolution X-ray optics 

Scientists in Japan have developed a high-resolution X-ray telescope sharp enough to distinguish an object just 3.5 mm wide from one kilometer away, by combining precision mirror-making technology with space astronomy. To test its performance, they built a first-of-its-kind evaluation system, capable of simulating starlight on the ground to measure the telescope’s sharpness before its launch on the US-Japan FOXSI sounding rocket mission. The findings, published in , represent a landmark achievement for Japanese X-ray astronomy and pave the way for high-resolution X-ray observations on future smaller satellites. ? 

Why do we need X-ray telescopes in space? 

Enormous amounts of X-rays are released by solar flares, exploding stars, and matter around black holes. These X-rays hold clues about some of the highest-temperature and most violent processes in the universe, but Earth’s atmosphere absorbs them before they reach the ground. Because scientists cannot study them from the surface, instruments must travel into space on balloons, sounding rockets, or satellites.

X-ray astronomers do it with high precision mirrors 

Achieving a high-resolution X-ray space telescope has been a challenge in Japanese X-ray astronomy. Two technical obstacles stood in the way: first was the telescope¡¯s mirror. X-rays do not reflect off ordinary surfaces. They can only be reflected at extremely small angles, and the mirror surface must be shaped to nanometer-level precision. Second was integration. Even a perfectly fabricated mirror can lose its precision during the process of mounting it into a telescope assembly. ? 
 
¡°The mirror is like a very precise funnel for X-rays. If any part of the funnel is even slightly out of place, the X-rays miss their target and the image blurs,¡± said Ikuyuki Mitsuishi, senior author and project leader from the at ºÚÁϳԹÏÍø. ¡°It must also survive the intense vibrations of a sounding rocket launch while retaining its optical precision.¡± 

From a synchrotron radiation facility to a space telescope 

SPring-8 is one of the world¡¯s most powerful X-ray research facilities, located in Hyogo Prefecture, Japan. Its particle accelerator produces very bright X-ray beams, known as synchrotron radiation, for scientific research. Scientists there had developed extremely precise mirror-making techniques to focus those X-ray beams. Those same techniques were used by the research team to build a high-resolution space telescope mirror. 

The researchers used a precision electroforming technique from SPring-8 to produce a nickel mirror, 60 mm in diameter and 200 mm tall. Unlike mirrors built from multiple pieces, this mirror was cast as a single seamless shell, so there were no joints or seams that could deflect the X-rays away from the focal point, and nothing could move out of place. 

The project brought together two very different areas of expertise: the astronomy team, led by researchers from ºÚÁϳԹÏÍø, worked on the optical design and the challenge of integrating the mirror into a space-ready telescope assembly. A team from the synchrotron radiation community, including members from SPring-8 as well as researchers from universities and industry, was responsible for precision mirror fabrication and building the ground-based testing system. ? 

Before launch, the researchers had to prove that the telescope worked on the ground, but this created a problem: to test a space telescope properly, you need to simulate starlight, and starlight arrives from so far away that its rays are almost perfectly parallel by the time they reach Earth. Recreating that on the ground is extremely difficult.  
 
The research team solved this by building a testing system at SPring-8. A very small X-ray source, just 10 micrometers across, was placed 900 meters away from the mirror. At that distance, the X-rays stayed parallel and closely mimicked the rays arriving from a real star.

¡°It¡¯s the first ground-based system capable of accurately evaluating the performance of high-resolution X-ray space telescopes at hard X-ray energies, and it is available to researchers worldwide who want to develop and test similar technology,¡± said Ryuto Fujii, first author and former master¡¯s student.

Launched into space with FOXSI-4 (and soon FOXSI-5) 

FOXSI is a collaborative sounding rocket experiment¡ªa small sounding rocket that carries instruments briefly into space. It is designed to capture X-ray images of the Sun¡¯s corona and flare. The program first launched in 2012 and its fifth flight is scheduled for 2026.???

The telescope was one of seven X-ray telescopes aboard FOXSI-4, which launched from Alaska on April 17, 2024, and successfully observed a solar flare in progress. Dr. Mitsuishi and his students were present at the launch. For the research team, this was a historic moment, the first time a domestically developed Japanese high-resolution X-ray telescope had flown as part of an international sounding rocket mission.?
?
The researchers also identified the main factor that limits further improvements in sharpness: tiny imperfections along the length of the mirror surface. This gives them a clear target for improvement in future mirrors.

A foundation for future space research 

This research shows that combining space astronomy and synchrotron radiation science can produce results that neither field could achieve alone. An improved version of the telescope is set to fly on the FOXSI-5 mission. 
 
The long-term goal is miniaturization. The research team aims to scale the mirror technology down to fit inside CubeSats, satellites about the size of a shoebox. High-resolution X-ray optics have not yet flown on CubeSats. If successful, this technology could make X-ray space observations much more accessible and open a new chapter in compact X-ray astronomy. 

Paper information:

Ryuto Fujii, Koki Sakuta, Kazuki Ampuku, Yusuke Yoshida, Makoto Yoshihara, Ayumu Takigawa, Keitoku Yoshihira, Tetsuo Kano, Naoki Ishida, Noriyuki Narukage, Keisuke Tamura, Kikuko Miyata, Gota Yamaguchi, Hidekazu Takano, Yoshiki Kohmura, Shutaro Mohri, Takehiro Kume, Yusuke Matsuzawa, Yoichi Imamura, Takahiro Saito, Kentaro Hiraguri, Hirokazu Hashizume, Hidekazu Mimura, and Ikuyuki Mitsuishi (2026). Development of Electroformed X-ray Optics Bridging Synchrotron Technology and Space Astronomy, Publications of the Astronomical Society of the Pacific, 138(4). DOI:  

Funding information: 

This work was supported by the Grants-in-Aid for Scientific Research (KAKENHI) from the Japan Society for the Promotion of Science (JSPS) under grant numbers JP22K18274, JP20K20920, JP23H00156, JP22H00134, and JP21KK0052, and JST SPRING (grant number JPMJSP2125). Additional support was received from the ISAS program for small-scale projects, Iwadare Scholarship Foundation, Yokoyama Scholarship Foundation, Hattori International Scholarship Foundation (HISF), and the THERS Make New Standards Program for the Next Generation Researchers. 

Expert contact:

Ikuyuki Mitsuishi 
Graduate School of Science   
ºÚÁϳԹÏÍø   
E-mail: mitsuisi@u.phys.nagoya-u.ac.jp 

Media contact: 

Merle Naidoo   
International Communications Office   
ºÚÁϳԹÏÍø   
Email: icomm_research@t.mail.nagoya-u.ac.jp 

Top image:

A color-coded X-ray image from ground-based testing at SPring-8 shows the X-ray optics successfully focusing X-rays onto a sharp central point. Yellow-green indicates the highest X-ray concentration, while blue represents lower intensity. Credit: Fujii et al., 2026

The origins of a debilitating muscle-wasting disease begin at birth, not in adulthood, ºÚÁϳԹÏÍø researchers have shown. A single treatment at this early stage significantly reduced nerve cell breakdown in adult mice. ? 

Spinal and Bulbar Muscular Atrophy (SBMA) is a rare inherited disease that causes progressive muscle weakness and wasting in men. Patients typically develop early symptoms such as hand tremors in their thirties, but diagnosis usually occurs around age 40 when muscle weakness becomes more evident. Because the disease is triggered by high levels of testosterone, only males are affected.  
 
Researchers at ºÚÁϳԹÏÍø have found that a natural burst of testosterone right after birth causes a mutant protein to overactivate the nerve cells that control muscles (motor neurons) in newborn mice carrying the SBMA mutation. This ongoing overactivation eventually causes those nerve cells to break down in adulthood. The findings, published in , showed that treatment given at birth significantly reduced this breakdown. 

While it is well established that abnormal protein accumulation in neurodegenerative diseases begins years or decades before symptoms appear, what actually happens in the body during this period remains poorly understood. This study focused on the earliest stage of SBMA, the first days after birth.  
 
A brief natural spike in testosterone known as the neonatal testosterone surge or ¡°mini-puberty¡± occurs in all newborn males and lasts approximately 10 days in mice and around 6 months in humans. Because the defective protein produced by the SBMA mutation¡ªmutant androgen receptor protein¡ªrequires testosterone to move into the nucleus of motor neurons and cause damage, the team suspected that this surge represented the earliest moment at which the disease could be triggered. 
 
¡°We confirmed that mutant protein accumulates in the nuclei of motor neurons in male SBMA mice within the first day of life, driven by the neonatal testosterone surge. Female mice with the same mutation showed no such effects, confirming that testosterone is the key trigger,¡± said lead author and assistant professor Tomoki Hirunagi from ºÚÁϳԹÏÍø¡¯s .

Additionally, genes responsible for activating nerve cells, especially glutamate receptors, were abnormally overactive in SBMA mice in the first week of life and caused motor neurons to become overactive. Importantly, the same abnormal overactivity was also observed in motor neurons grown in the laboratory from the cells of actual SBMA patients. This suggests that the disease process in humans may follow the same pattern.

?To test whether treating the disease at birth could help, the researchers administered two gene-silencing drugs to newborn mice with the SBMA mutation, one targeting the mutant protein directly, and one targeting REST4, a protein found to drive the abnormal nerve cell overactivity.  
 
The drug targeting the mutant protein temporarily reduced mutant protein levels and the drug targeting REST4 corrected abnormal gene activity in motor neurons. Both treatments improved survival and motor performance, and decreased motor neuron degeneration in mice assessed at 13 weeks of age.  

¡°Perhaps the most remarkable finding was that a drug given at birth to target the mutant protein continued to protect motor neurons months later, even though the drug effects  had worn off within two weeks. This suggests that intervening at the right moment early in life can have lasting consequences, long after the treatment is gone,¡± Dr. Hirunagi said. 
 
REST4, the protein found to drive the abnormal nerve cell overactivity in SBMA, represents a potential new target for future therapies. 

ºÚÁϳԹÏÍø has previously developed leuprorelin acetate, the only drug approved in Japan for SBMA treatment, making these discoveries part of a broader research legacy in tackling the disease. 
 
The research team identified the next priority as determining whether the same abnormal nerve cell overactivity occurs in human SBMA patients. ¡°This is currently very difficult to study directly, because examining newborn nervous system activity in living patients is not feasible. Our goal is to translate these findings into patient care,¡± Dr. Hirunagi said. The team also intends to evaluate the safety of gene-silencing drugs and the efficacy of repeated treatment. 

Paper information:  

Tomoki Hirunagi, Kentaro Sahashi, Madoka Iida, Kazunari Onodera, Satoshi Yokoi, Yosuke Ogura, Genki Tohnai, Kenji Sakakibara, Kentaro Maeda, C. Frank Bennett, Yohei Okada, Masahisa Katsuno (2026). Restoring early postnatal synaptic dysregulation rescues motor neuron degeneration in a mouse model of Spinal and Bulbar Muscular Atrophy, Nature Communications, 17: 2412. DOI: .??

Funding information: 

This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant numbers: JP20H00527, JP23H00420, JP24K18683, JP23K24249, JP24K18712, JP25K02585) and the Japan Agency for Medical Research and Development (AMED) (Grant numbers: JP22nk0101575, JP22am0401007, JP22bm0804020, JP25bm1423003).

Expert contact:  

Tomoki Hirunagi   
Graduate School of Medicine  
ºÚÁϳԹÏÍø  
E-mail: hirunagi.tomoki.k3@f.mail.nagoya-u.ac.jp 

Masahisa Katsuno 
Graduate School of Medicine  
ºÚÁϳԹÏÍø 
E-mail: katsuno.masahisa.i1@f.mail.nagoya-u.ac.jp

Media contact:  

Merle Naidoo?
International Communications Office?
ºÚÁϳԹÏÍø?
Email: icomm_research@t.mail.nagoya-u.ac.jp

Top image:

Microscopy images of spinal cord tissue from male (left) and female (right) SBMA model mice on the first day after birth. Brown staining indicates accumulation of the mutant androgen receptor protein in motor neuron nuclei. The protein accumulates extensively in male mice but shows little to no accumulation in female mice, confirming that testosterone drives the early accumulation of the mutant protein in motor neurons. Credit: Hirunagi et al., 2026 

Fumagillin has been investigated as a drug lead for more than 70 years, but its more potent relative ovalicin was never developed. Now, scientists have identified metabolic instability as the key barrier and have overcome it through chem-bio hybrid synthesis, yielding drug candidates for amebiasis, a parasitic infection affecting 50 million people annually. 

Amebiasis is a parasitic disease caused by the microscopic protozoan Entamoeba histolytica. Infection occurs through the ingestion of cysts from contaminated water or food. Worldwide, approximately 50 million symptomatic cases are estimated annually, mainly in tropical and subtropical regions.??
?
Fumagillin, a fungal natural product, has been studied for decades as a potential antiparasitic drug, but its more potent relative ovalicin was never developed. Now, a study published in the reveals why: although ovalicin is highly active against amebiasis, liver enzymes rapidly break it down in the body. Researchers ?used a chem-bio hybrid approach to turn that insight into metabolically stable drug candidates that worked in animal models of amebiasis, including liver infection with abscess formation.?
?
The research team, led by scientists from the at ºÚÁϳԹÏÍø, ?identified the liver cytochrome P450 enzymes responsible for ovalicin breakdown, with CYP 2B1 and CYP 2C6 emerging as the main drivers. Blocking these enzymes with a chemical inhibitor significantly prolonged ovalicin survival, providing strong evidence that rapid liver metabolism limits its effectiveness.?

Successfully curing infections in animals 

¡°We engineered fungi to build modified ovalicin molecules with a special attachment point that we could customize. We then clipped different molecular groups onto that point to create versions that the liver could not destroy,¡± explained senior author and associate professor Yuta Tsunematsu.  
 
Using genetically engineered filamentous fungi, the team produced gram-scale quantities of a non-natural ovalicin molecule. They then created about 30 derivatives and tested each one to find versions that killed parasites, survived liver breakdown, and were not toxic. 
 
The protozoan parasite depends on an enzyme called MetAP2 for its proteins to work properly and survive. Blocking MetAP2 kills it but does not harm humans because we have a backup enzyme that can perform the same function. 
 
Two of the new compounds, YOK24 and NS-181, blocked the parasite¡¯s MetAP2 enzyme and eliminated the parasitic infection in hamsters, causing liver abscesses to disappear entirely. 
 
These results are an important step toward testing these drug candidates in humans. Importantly, the compounds were effective after both injection and oral administration. Oral treatment would be especially valuable in low-resource settings, where amebiasis is most prevalent. 

A new drug development method 

Current amebiasis treatments, such as metronidazole, can cause side effects and face growing concerns about drug resistance. 
 
This study introduces Chem-Bio Hybrid Synthesis, a new method that combines genetic engineering of microbes and chemistry to transform natural compounds that worked in lab tests but failed in patients due to rapid breakdown or toxicity. The approach could address these challenges for amebiasis and be applied to develop treatments for other parasitic diseases, cancer, and obesity. 

Paper information:  

Yuki Okura, Yumiko Saito-Nakano, Andrii Balia, Nurul Syahmin Binti Suhaimi, Chika Ando, Namiko Ogata, Tomona Ikeda, Takumi Sato, Keiko Kano, Emi Mishiro-Sato, Masaki Kita, Noriyuki Miyoshi, Kenji Watanabe, Kouichi Yoshinari, Norio Shibata, Mihoko Mori, Seiki Kobayashi, Yuji Sumii, Ryota Shizu, Tomoyoshi Nozaki, Yuta Tsunematsu (2026). Chem¨CBio Hybrid Synthesis Enables Reengineering of Natural Product-Based Methionine Aminopeptidase 2 Inhibitors for Treating Amebiasis, Journal of the American Chemical Society, 148(7), 7189¨C7201. DOI: . 

Funding information:

This work was financially supported by the Japan Agency for Medical Research and Development (AMED) (Grant numbers: JP22wm0325020, JP23wm0325070, JP25jm0110022) and the Japan Society for the Promotion of Science (JSPS) (Grant number 24K02190). 

Expert contact: 

Yuta Tsunematsu 
Graduate School of Bioagricultural Sciences 
ºÚÁϳԹÏÍø 
E-mail: tsunematsu.yuta.p4@f.mail.nagoya-u.ac.jp 

Media contact:

Merle Naidoo?
International Communications Office?
ºÚÁϳԹÏÍø?
Email: icomm_research@t.mail.nagoya-u.ac.jp 

Top image:

Scientists genetically engineered the fungus Aspergillus nidulans to produce a modified ovalicin molecule. Although this molecule itself was still susceptible to liver breakdown, it provided a chemical handle that enabled the synthesis of metabolically stable drug candidates for amebiasis. Credit: Yuta Tsunematu, ºÚÁϳԹÏÍø?

ºÚÁϳԹÏÍø researchers used iron and blue LEDs to synthesize natural molecules, cutting the need for expensive chiral components by two-thirds.

Photocatalysts facilitate chemical reactions by absorbing light. Metal-based photocatalysts are widely used in organic synthesis due to their durability and the ability to tune their function by modifying the ligands attached to the central metal atom.

Most metals used in photocatalysts, such as ruthenium and iridium, are rare and expensive. Researchers at ºÚÁϳԹÏÍø, Japan, previously developed an iron-based alternative, but it required large amounts of costly chiral ligands, which act as spatial templates to determine the three-dimensional structure of chemical products.

In a recent study published in the, the researchers developed an iron catalyst that reduces the use of chiral ligands by two-thirds and enables photocatalytic reactions under energy-efficient blue LED light.

Using this new catalyst, they completed the asymmetric total synthesis of (+)-heitziamide A, a natural compound from medicinal plants that suppresses respiratory bursts.

Professor , Assistant Professor , and graduate student Hayato Akao at ºÚÁϳԹÏÍø’s Graduate School of Engineering developed this technology.

Redefining the design of iron catalysts

In , the researchers developed an iron photocatalyst that used three chiral ligands per iron atom, but only one-third of these ligands contributed to enantioselectivity, making the process inefficient.

Meanwhile, the newly developed iron photocatalyst combines cost-effective achiral bidentate ligands with chiral ligands to target a specific iron(III) salt structure. The chiral ligand controls the three-dimensional configuration, while the achiral bidentate ligand tunes the catalytic activity.

Using this catalyst, researchers achieved a precise radical cation (4 + 2) cyclization, joining two molecules to form a hexagonal ring. This method enables the synthesis of 1,2,3,5-substituted adducts, structures common in natural products such as heitziamide A.

“The new catalyst design represents the definitive form of chiral iron(III) photoredox catalysts,” stated Ohmura, one of the study’s corresponding authors. “We believe this achievement marks a significant milestone in advancing iron-based photocatalysis.”

Advancing artificial synthesis of (+)-heitziamide A

While artificial synthesis of heitziamide A has been previously reported, the total asymmetric synthesis of its natural enantiomer has not yet been achieved.

Using selective six-membered-ring formation with an iron photocatalyst activated by blue light, the researchers achieved the first total asymmetric synthesis of (+)-heitziamide A. This indicates that using the mirror-image catalyst would also allow the synthesis of (-)-heitziamide A, thereby enabling the selective production of both enantiomers.

Significance and future perspectives

The newly developed iron photocatalyst enables the precise synthesis of complex molecules, including pharmaceutical precursors, using abundant iron and blue LEDs instead of rare metals.

“Achieving the first-ever asymmetric total synthesis of (+)-heitziamide A using this catalytic reaction is a remarkable accomplishment,” stated Ishihara, the study’s other corresponding author. “Several additional bioactive substances can be accessed through total synthesis, with enantioselective radical cation (4 + 2) cycloaddition serving as a key step. We intend to publish follow-up papers on the asymmetric total synthesis of these compounds in the near future.”

Paper information:

Hayato Akao, Shuhei Ohmura, and Kazuaki Ishihara (2026). A Rational Design of Chiral Iron(III) Complexes for Photocatalytic Asymmetric Radical Cation (4 + 2) Cycloadditions and the Total Synthesis of (+)-Heitziamide A, Journal of the American Chemical Society.

Funding information:

This work was supported by JSPS KAKENHI grants 24K17677 and 23H05467.

Expert contact:

Kazuaki Ishihara
Graduate School of Engineering, ºÚÁϳԹÏÍø
ishihara.kazuaki.s7@f.mail.nagoya-u.ac.jp

Media contact:

Naomi Inoue
International Communications Office, ºÚÁϳԹÏÍø
icomm_research@t.mail.nagoya-u.ac.jp

Top image:

The newly designed iron photocatalyst (front) and the previous catalyst (back)
(Credit: Yuzuru Endo)

Two bacteria working together to break down intestinal mucus are identified as a contributing factor to chronic constipation

Scientists at ºÚÁϳԹÏÍø in Japan have found two gut bacteria working together that contribute to chronic constipation. The duo, Akkermansia muciniphila and Bacteroides thetaiotaomicron, destroy the intestinal mucus coating essential for keeping the colon lubricated and feces hydrated. Their excess degradation leaves patients with dry, immobile stool. This discovery, published in , finally explains why standard treatments often fail for millions of people with chronic constipation.

Notably, the study shows that Parkinson’s disease patients, who suffer from constipation decades before developing tremors, have higher levels of these mucus-degrading bacteria. While constipation in Parkinson¡¯s disease has traditionally been attributed to nerve degradation, these findings suggest that bacterial activity also plays a crucial role in the development of their symptoms.

Why ¡°mucin¡± matters for digestion

Constipation is a very common digestive problem. Doctors have assumed it happens because of slow gut movement when our intestines are not moving food along fast enough. However, this explanation does not work for everyone.

Some people have constipation with no identifiable cause, referred to as chronic idiopathic constipation (CIC). Parkinson’s disease patients also face severe, treatment-resistant constipation, though it is clinically categorized separately from CIC. Many struggle with severe constipation for 20 or 30 years before they develop tremors and movement problems, but researchers did not know why until now.

Instead of focusing on nerve and muscle movement in the gut, the researchers examined the protective gel-like coating called colonic mucin, a substance in the large intestine that lines the intestinal walls and is found within stool. Colonic mucin keeps stool moist, helps it move smoothly through our digestive tract, and protects the intestinal wall from bacteria.

They found that two gut bacteria work in sequence to break down this mucin. B. thetaiotaomicron uses enzymes to remove protective sulfate groups from the mucin, and A. muciniphila then breaks down and consumes the exposed mucin.

Sulfate groups attached to colonic mucin molecules normally prevent bacteria from degrading them. When too much mucin is destroyed, stool loses moisture and becomes hard and dry, causing constipation. Because the problem is mucin loss, not slow gut movement, standard laxatives and gut motility drugs are often ineffective.

A new frontier for gut health treatment

¡°We genetically modified B. thetaiotaomicron so it could no longer activate the enzyme sulfatase that removes sulfate groups from mucin,¡± Tomonari Hamaguchi, lead author and lecturer from the Academic Research & Industry-Academia-Government Collaboration Office at ºÚÁϳԹÏÍø explained.

¡°We put these modified bacteria into germ-free mice together with Akkermansia muciniphila, and surprisingly the mice did not develop constipation; the mucin stayed protected and intact.¡±

The experiment proved that blocking the sulfatase enzyme prevents the bacteria from degrading mucin. Therefore, drugs that block sulfatase could treat bacterial constipation in humans.

For millions of patients with treatment-resistant constipation, including those with Parkinson’s disease, this discovery offers hope for new therapies that address the root microbial causes of their condition.

Paper Information:

Tomonari Hamaguchi, Noriaki Gibo, Misuzu Ohara, Mikako Ito, Tomoyuki Ogura, Jun-Ichi Takeda, Hiroshi Nishiwaki, Fei Zhao, Ryo Kinoshita-Daitoku, Masashi Hattori, Koji Nonogaki, Tetsuya Maeda, Kenichi Kashihara, Yoshio Tsuboi, Masaaki Hirayama, Mitsuhiro Fujishiro, Hiroki Kawashima, Kinji Ohno (2026). Bacterial constipation: Mucin-degrading intestinal commensal bacteria cause constipation, Gut Microbes, 18(1).

Funding information:

This work was supported by Grants-in-Aids from the Japan Agency for Medical Research and Development (AMED) (JP23ek0109678) and the Japan Society of the Promotion of Science (JSPS) (JP22K15394, JP22K17343, JP23H02794, JP23K18273, and JP23K06412), and by grants from the Hori Sciences and Arts Foundation and from Yakult Bio-Science Foundation.

Expert Contact:

Tomonari Hamaguchi
Academic Research & Industry-Academia-Government Collaboration
ºÚÁϳԹÏÍø
Email: hamaguchi.tomonari.r4@f.mail.nagoya-u.ac.jp

Media contact:

Merle Naidoo
International Communications Office
ºÚÁϳԹÏÍø
Email: icomm_research@t.mail.nagoya-u.ac.jp

Top image:

The two bacteria that cause bacterial constipation, seen under an electron microscope. Left: Bacteroides thetaiotaomicron (Top: Transmission Electron Microscopy (TEM) image; Bottom: Scanning Electron Microscopy (SEM) image; Right: Akkermansia muciniphila (Top: TEM; Bottom: SEM). They work in sequence to destroy the intestinal mucus coating that keeps stool moist. Credit: Tomonari Hamaguchi, ºÚÁϳԹÏÍø

Now researchers can pinpoint which brain circuits drive social behaviors by manipulating specific individuals in real time, even when multiple animals closely interact  

A male fruit fly in a laboratory chamber extends his wings and vibrates them to produce his species’ version of a love song. A female fly stays nearby listening. Suddenly, a green light flashes across the chamber for a fraction of a second. The male’s song cuts off mid-note and his wings fold. The female, not impressed by the interrupted serenade, walks away. The culprit? An AI system that watched the male begin his courtship dance and shut down his song-producing brain cells. 

Developed by scientists at ºÚÁϳԹÏÍø and their collaborators from Osaka University and Tohoku University, the AI can watch and recognize animal behaviors and control the specific brain circuits that drive them. Published in , the study presents an advanced AI system that can identify which animal performs a behavior in a group and selectively target only that animal¡¯s brain cells during social interactions.

YORU (Your Optimal Recognition Utility) recognizes different behaviors across species with over 90% accuracy, including food-sharing between ants, social orientation in zebrafish, and grooming in mice. However, the real breakthrough came with fruit flies, when the research team combined YORU with brain control technology to shut off song-producing neurons during courtship, which reduced male mating success. 

Traditional behavior analysis tracks individual body parts frame by frame, similar to motion capture technology in video games. This method is challenging when multiple animals interact or overlap. Additionally, scientists needed faster tools for real-time experiments where split-second timing is critical.

¡°Instead of tracking body points over time, YORU recognizes entire behaviors from their appearance in a single video frame. It spotted behaviors in flies, ants, and zebrafish with 90-98% accuracy and ran 30% faster than competing tools,¡± Hayato Yamanouchi, co-first author from ºÚÁϳԹÏÍø¡¯s said. 

Senior author Azusa Kamikouchi explained that the real breakthrough combines YORU with optogenetics, using light to control genetically engineered neurons. ¡°We can silence fly courtship neurons the instant YORU detects wing extension. In a separate experiment, we used targeted light that followed individual flies and blocked just one fly’s hearing neurons while others moved freely nearby.¡±

Watch how YORU works: YORU identifies the exact moment a male fruit fly extends his wing to court a female¡ªdetecting courtship behavior in real time. Credit: Yamanouchi et al., 2026 
 
This individual-focused control solves a major challenge: previous methods could only illuminate entire chambers, which affected all animals at the same time and made it impossible to study an individual’s role during social interactions. 

How the brain control technology works 

Step 1: Genetic engineering  
The scientists genetically modify the animals to have special light-sensitive proteins (called “opsins”) expressed in specific neurons in their brains. These proteins can turn neurons on or off, depending on the type. 

Step 2: Detection and response 
? YORU captures the animal’s behavior in real-time with a camera 
? When YORU’s AI detects the target behavior, it instantly sends an electrical signal to a light source 
? The light automatically turns on and shines on the target animal

Step 3: Light controls the brain 
? The light hits the target animal and reaches those genetically modified neurons 
? The light-sensitive proteins respond to the light by opening an ion channel on the membrane of target neurons 
? This blocks or activates those specific neurons, changing the animal’s brain activity 
? The behavior is affected as a result 
 
YORU works across species, can be trained to recognize new behaviors with minimal training data, and requires no programming skills to use. The Nagoya team made YORU available online for scientists worldwide studying how brains control social interactions.

Paper Information: 

Hayato M. Yamanouchi, Ryosuke F. Takeuchi, Naoya Chiba, Koichi Hashimoto, Takashi Shimizu, Fumitaka Osakada, Ryoya Tanaka, and Azusa Kamikouchi (2026). YORU: animal behavior detection with object-based approach for real-time closed-loop feedback, Science Advances., 12(7). ???

Expert Contact: 

Azusa Kamikouchi
Graduate School of Science
ºÚÁϳԹÏÍø
Email: kamikouchi.azusa.r4@f.mail.nagoya-u.ac.jp

Media contact:

Merle Naidoo
International Communications Office
ºÚÁϳԹÏÍø
Email: icomm_research@t.mail.nagoya-u.ac.jp

Top image:

ºÚÁϳԹÏÍø scientists develop an AI system to automatically identify behavior types and control individual animals’ brain cells during group interactions. Credit: Yamanouchi et al., 2026

This technique also eliminates the need for fluorocarbon gases, which have significant global warming potentials.

After more than a decade of research and development, Tokyo Electron Miyagi Ltd. has introduced an innovative semiconductor etching method that achieves etch rates up to five times faster than conventional processes. Now, a collaborative research team from ºÚÁϳԹÏÍø and the company has examined the underlying etching mechanisms responsible for this enhanced performance.

This new method employs plasma etching with hydrogen fluoride (HF) at very low temperatures. In contrast to conventional fluorocarbon etching gases, which have high global warming potentials (GWPs), HF has a substantially lower GWP.

The study demonstrated that this process significantly reduces processing time and enhances energy efficiency, particularly for etching complex three-dimensional (3D) structures in advanced devices, such as gate-all-around (GAA) transistors and 3D NAND flash memory chips. The findings were published in the .

Semiconductor etching is an essential chip-manufacturing process that selectively removes material from a wafer surface to form precise circuit patterns. Reactive ion etching technologies have played a pivotal role in wafer fabrication through synergistic reactions between chemical gases and ions.

However, ongoing miniaturization of semiconductor devices poses substantial challenges for etching techniques, especially in delivering chemical species deep into complex 3D structures with high aspect ratios, where the depth is much greater than the width. These difficulties have led to a considerable decrease in “etching throughput,” the amount of etching work done in a particular period of time.

To address these challenges, a ºÚÁϳԹÏÍø research team, led by Professors and of the , collaborated with , a manufacturer of plasma etching equipment, to verify that this new etching process mechanism significantly enhances throughput.

Previous studies have indicated that cooling the substrate to ultra-low temperatures substantially increases etch rates in silicon-based materials, such as silicon dioxide (SiO?) films. Furthermore, it has been suggested that co-absorption of HF and the etching reaction product, water (H?O), significantly enhances surface reactions at very low temperatures.

“However, precise synergistic interactions between HF ions, surface-adsorbed HF and H?O, and the material surface being etched for cryogenic plasma etching remain unclear,” stated Professor Hsiao. “Therefore, we assessed the performance of etching SiO? films using HF plasma at very low temperatures.”

The researchers cooled the semiconductor substrate to ?60¡ãC and then exposed it to an HF plasma. They observed that both HF and H?O adsorbed onto the SiO? surface and found that H?O acts as a catalyst, reducing the etching activation barrier to nearly zero.

The study also demonstrated that increasing ion irradiation energy promotes the generation of H?O, which subsequently adsorbs onto the surface, accelerating a self-catalytic cycle that attracts HF. Interestingly, this process, referred to as an ion-enhanced surface autocatalytic reaction, resulted in an exponential increase in the film etching rate per unit of ion energy.

The study confirmed that this new process achieves an etching throughput for SiO? films approximately 100 times greater than that attained under conventional room-temperature and low-ion-energy conditions.

“Furthermore, the use of HF plasma instead of conventional fluorocarbon gases, which typically exhibit high global warming potentials, eliminates the carbon footprint associated with the etching process,” stated Professor Hsiao.

“Through this industry collaboration, we are advancing verification in an environment similar to actual manufacturing equipment. We aim to apply this process to semiconductor manufacturing lines and extend its use to broader production processes.”

Paper information:

Shih-Nan Hsiao, Yusuke Imai, Makoto Sekine, Ryutaro Suda, Yuki Iijima, Yoshihide Kihara, Kenji Ishikawas, and Masaru Hori (2025). Revolutionizing reactive ion etching: ion-enhanced surface autocatalytic reactions enabling ultra-high throughput using cryogenic hydrogen-fluoride plasma. Chemical Engineering Journal.
DOI:

Expert contact:

Shih-Nan Hsiao
Center for Low-temperature Plasma Sciences
Email: hsiao.shih.nan.t8@f.mail.nagoya-u.ac.jp

Media contact:

Naomi Inoue
International Communications Office, ºÚÁϳԹÏÍø
Email: icomm_research@t.mail.nagoya-u.ac.jp

Top image:

Synergy of ion-enhanced and surface adsorbed HF/H₂O for etching
(Credit: Shih-Nan Hsiao)

ºÚÁϳԹÏÍø researchers break conventional rules to develop heat-resistant, recyclable metal alloys for automotive and aerospace use.

Aluminum is prized for being lightweight and strong, but at high temperatures it loses strength. This has limited its use in engines, turbines, and other applications where parts must stay strong under high temperature conditions. Researchers at ºÚÁϳԹÏÍø have developed a method that uses metal 3D printing to create a new aluminum alloy series optimized for high strength and heat resistance. All new alloys use low-cost, abundant elements, and are recycling-friendly, with one variant staying both strong and flexible at 300¡ãC. The study was published in . 

Breaking with tradition to create the perfect aluminum alloy

¡°The design centers on iron, which metallurgists usually don¡¯t add to aluminum because it makes the metal brittle and vulnerable to corrosion,¡± Naoki Takata, lead author and professor at ºÚÁϳԹÏÍø , explained.

¡°The extreme cooling rates in laser powder bed fusion, which is a representative process of metal 3D printing technologies, cause molten metal to solidify in seconds. This changes fundamental rules¡ªthe rapid cooling traps iron and other elements in arrangements (formation of metastable phases) that can¡¯t form under normal manufacturing conditions. By carefully selecting which elements to add, we created new alloys that are both heat-resistant and strong.¡±

The researchers developed a systematic method to predict which elements will strengthen the aluminum matrix and which will form protective micro or nano structures. They tested these predictions by creating new alloys with copper, manganese, and titanium, and then confirmed the results through electron microscopy.

The best performing alloy contains aluminum, iron, manganese, and titanium (Al-Fe-Mn-Ti), and outperforms all other 3D-printed aluminum materials by combining strength at high temperatures with flexibility at room temperature.

¡°Our method relies on established scientific principles about how elements behave during rapid solidification in 3D printing and is applicable to other metals. The alloys also proved easier to 3D print than conventional high-strength aluminum, which frequently cracks or warps during fabrication,¡± Professor Takata noted.

Watch how advanced aluminum alloys are made using 3D printing. ?This video shows a laser melting metal powder layer by layer to create strong, lightweight aluminum parts. Copper, manganese, and titanium are added to improve strength, durability, and performance. Credit: Aichi Center for Industry and Science and Technology, Toyota

Lighter vehicles, fewer emissions 

The new materials could enable lightweight aluminum components in parts that operate at elevated temperatures, such as compressor rotors and turbine components. Lighter vehicles consume less fuel and produce fewer emissions. 
 
The aerospace industry may also benefit, as aircraft engines require materials that combine light weight with heat resistance. Beyond these applications, the research provides a framework for designing new classes of metals specifically for 3D printing, with potential to accelerate development across multiple industries.

Paper information: 

Naoki Takata, Koki Minamihama, Takanobu Miyawaki, Yue Cheng, Yifan Xu, Wenyuan Wang, Dasom Kim, Asuka Suzuki, Makoto Kobashi, and Masaki Kato (2025). Design of high-performance sustainable aluminum alloy series for laser additive manufacturing. Nature Communications, 16, 11105. DOI:

Funding information: 

This research was supported by JST PRESTO (Grant JP22688912) and JSPS KAKENHI (Grant 24H00378).

Research Contact: 

Naoki Takata 
Graduate School of Engineering 
ºÚÁϳԹÏÍø 
Email: takata.naoki@material.nagoya-u.ac.jp

Media Contact: 

Merle Naidoo
International Communications Office
ºÚÁϳԹÏÍø
Email: icomm_research@t.mail.nagoya-u.ac.jp

Top image:

Microscope image showing the layered structure of a new 3D-printed aluminum alloy. The wave-like patterns are ¡°melt pools,¡± traces left by the laser as it melted metal powder layer by layer. The small dark dots are nanoscale particles that give the alloy its exceptional strength and heat resistance. Credit: Takata et al., 2025 

ºÚÁϳԹÏÍø researchers develop first GeSn-based Group IV resonant tunneling diode that operates at room temperature.

In a world first, researchers at ºÚÁϳԹÏÍø in Japan have successfully developed a resonant tunnel diode (RTD) that operates at room temperature made entirely from Group IV semiconductor materials. The development of an RTD that operates at room temperature means the device could be deployed at scale for next-generation wireless communication systems. The use of only non-toxic Group IV semiconductor materials also supports more sustainable manufacturing processes.

This research marks a pivotal step toward terahertz wireless components that deliver unprecedented speed and data handling capacity with superior energy efficiency. ¡°Compared to InGaAs-based Group III-V RTDs that include toxic and rare elements, such as indium and arsenic, Group IV compounds-based RTDs are safer, lower cost, and offer advantages for creating integrated production processes,¡± said senior author Dr. Shigehisa Shibayama from the ºÚÁϳԹÏÍø . The results were published in the journal .

Terahertz waves and quantum devices

Researchers have long struggled to achieve the high-speed and large-volume data transfer needed for sixth-generation (6G) cellular networks. One promising solution is wireless communication using terahertz waves¡ªelectromagnetic waves that vibrate a trillion times per second, enabling ultra-high-speed data transmission. However, many technical challenges remain before this technology can be made practical for consumer applications.

A critical component for realizing terahertz communication is the RTD. This quantum device operates through negative differential resistance, a counterintuitive property where increasing voltage actually decreases current. When part of a properly designed circuit, this property allows the diodes to sustain high-frequency oscillations that would otherwise decay due to electrical losses.

Moving beyond laboratory constraints

The secret behind an RTD lies in its double-barrier structure, where electrons or holes tunnel through layers of different semiconductor materials, each only a few atoms thick. These layers have mainly been created from InGaAs-based Group III-V materials that include toxic and rare elements, such as indium and arsenic.

In previous research by the same group, the researchers created a p-type RTD using only Group IV materials, specifically germanium-tin (GeSn) and germanium-silicon-tin (GeSiSn) alloys. One limitation was that the diode only functioned at extremely low temperatures, around -263¡ãC. Since consumer electronics and wireless systems cannot practically reach this level of cooling, the device would have remained a laboratory curiosity.

Shibayama and his colleagues have now discovered how to use only Group IV materials to produce a p-RTD that functions at room temperatures of around 27¡ãC. This significant improvement opens new possibilities for the widespread adoption of terahertz semiconductor devices.

The research group achieved its breakthrough by introducing hydrogen gas during the layer formation process. They tested three different scenarios: 1) introducing hydrogen gas to both the two GeSiSn layers and three GeSn layers, 2) introducing no hydrogen gas, and 3) introducing hydrogen gas to only the three GeSn layers. In the last scenario, hydrogen gas restricted island growth and mixing between layers, resulting in a smooth and well-ordered double-barrier structure.

¡°The RTD cannot function if these layers are mixed,¡± said Dr. Shibayama. ¡°If there are defects in the layers, electrons can tunnel through these easier routes, leading to current leakage. This leakage current needs to be reduced for negative differential resistance¡ªthe key property of an RTD¡ªto occur.¡±

Publication:
Shota Torimoto, Shuto Ishimoto, Yoshiki Kato, Mitsuo Sakashita, Masashi Kurosawa,
Osamu Nakatsuka, & Shigehisa Shibayama. (2025). Room temperature operation of Ge_1?xSn_x/Ge_1?x?ySi_xSn_y resonant tunneling diode featured with H₂-introduction during molecular beam epitaxy. ACS Applied Electronic Materials, 7(16), 7688¨C7696.

Funding:
This research was supported in part by JST PRESTO (Grant Number JPMJPR21B6) and JST CREST (Grant Number JPMJCR21C2).

Expert contact:
Shigehisa Shibayama
ºÚÁϳԹÏÍø, Graduate School of Engineering
s-shibayama@nagoya-u.jp

Media contact:
Alexander Evans
ºÚÁϳԹÏÍø, International Communications Office
icomm_research@t.mail.nagoya-u.ac.jp

Top image: Assistant Professor Shigehisa Shibayama (right) and first author Shota Torimoto (left), along with the rest of the team, have developed a resonant tunneling diode using only non-toxic Group IV semiconductor materials that operates at room temperature. Credit: Shigehisa Shibayama (ºÚÁϳԹÏÍø) and Shota Torimoto (ºÚÁϳԹÏÍø)