Genome language models produce first generative design of viable bacteriophage genomes and yielded 16 viable phages

Amazing stuff! This could be a breakthrough!

"... Researchers ... used an AI model called Evo 2 to design 16 viable bacteriophages, that is, viruses that infect bacteria—the first time AI has generated whole living genomes. ..."

"Scientists have created the first ever viruses designed by artificial intelligence (AI), and they’re capable of hunting down and killing strains of Escherichia coli (E. coli). ..."

From the abstract:

"Many important biological functions arise not from single genes, but from complex interactions encoded by entire genomes. Genome language models have emerged as a promising strategy for designing biological systems, but their ability to generate functional sequences at the scale of whole genomes has remained untested.

Here, we report the first generative design of viable bacteriophage genomes. We leveraged frontier genome language models, Evo 1 and Evo 2, to generate whole-genome sequences with realistic genetic architectures and desirable host tropism, using the lytic phage ΦX174 as our design template.

Experimental testing of AI-generated genomes yielded 16 viable phages with substantial evolutionary novelty. Cryo-electron microscopy revealed that one of the generated phages utilizes an evolutionarily distant DNA packaging protein within its capsid. Multiple phages demonstrate higher fitness than ΦX174 in growth competitions and in their lysis kinetics. A cocktail of the generated phages rapidly overcomes ΦX174-resistance in three E. coli strains, demonstrating the potential utility of our approach for designing phage therapies against rapidly evolving bacterial pathogens. This work provides a blueprint for the design of diverse synthetic bacteriophages and, more broadly, lays a foundation for the generative design of useful living systems at the genome scale."

Doomslayer: Progress Roundup - by Malcolm Cochran

How We Built the First AI-Generated Genomes (original news release)

World’s first AI-designed viruses a step towards AI-generated life (partial open access) "Scientists used AI to write coherent viral genomes, using them to synthesize bacteriophages capable of killing resistant strains of bacteria."

Generative design of novel bacteriophages with genome language models (preprint, open access)

"Going from designing individual genes to complete genomes is an incredibly challenging problem. We have previously shown that the genomic foundation models like the Evo series can generate single proteins and multi-component systems like CRISPR-Cas complexes or protein-protein interactions. However, even before we developed Evo, one of our longstanding goals has been to design a complete, functional genome with a biological language model."

"The genome of ΦX174 is also historically significant. In 1977, it was the first complete genome ever sequenced by Fred Sanger and colleagues. In 2003, it was the first whole genome ever chemically synthesized, proving that genomes could be assembled from scratch, by Craig Venter and colleagues. Now, in 2025, we have used ΦX174 as a template to produce the first AI-generated genomes. This progression represents the fundamental capabilities that define modern genomics: we learned to read DNA, then to write it, and now to design it."

Fig. 1 Evo composes realistic bacteriophage genomic sequences.

Fig. 2 Generative design of novel bacteriophages with target host tropism.

Starting a fluorescent biosensor revolution

Good news!

"Now, a collaborative research team ... has developed a synthetic biology platform to streamline the discovery, molecular evolution, and cost-effective manufacturing of small and highly efficient nanosensors that can detect specific proteins, peptides, and small molecules by increasing their fluorescence up to 100-fold in less than a second. As a key component, the platform uses new fluorogenic amino acids (FgAAs) that can be encoded into target-binding small protein sequences (binders) with the help of an innovative methodology that enables the in vitro expansion of the genetic code. Through a process of high-throughput sensor screening, validation, and directed evolution, the platform enables the rapid and cost-effective transformation of protein binders into high-contrast nanosensors for a wide range of applications in fundamental research, environmental monitoring, medical diagnostics and augmented therapeutics. ..."

From the absract:

"Binding-activated optical sensors are powerful tools for imaging, diagnostics, and biomolecular sensing. However, biosensor discovery is slow and requires tedious steps in rational design, screening, and characterization. Here we report on a platform that streamlines biosensor discovery and unlocks directed nanosensor evolution through genetically encodable fluorogenic amino acids (FgAAs). Building on the classical knowledge-based semisynthetic approach, we engineer ~15 kDa nanosensors that recognize specific proteins, peptides, and small molecules with up to 100-fold fluorescence increases and subsecond kinetics, allowing real-time and wash-free target sensing and live-cell bioimaging. An optimized genetic code expansion chemistry with FgAAs further enables rapid (~3 h) ribosomal nanosensor discovery via the cell-free translation of hundreds of candidates in parallel and directed nanosensor evolution with improved variant-specific sensitivities (up to ~250-fold) for SARS-CoV-2 antigens. Altogether, this platform could accelerate the discovery of fluorogenic nanosensors and pave the way to modify proteins with other non-standard functionalities for diverse applications."

Starting a fluorescent biosensor revolution "Molecular biosensors that only light up upon binding their targets open vast possibilities for medical diagnostics, fundamental research, environmental monitoring, and more"

Rapid discovery and evolution of nanosensors containing fluorogenic amino acids (open access)

Fig. 1: A platform to discover, evolve, and produce FgAA-containing NS.

Binding-activated biosensors exposed to an “excitation light” of a specific wavelength only emit fluorescent light of a different fluorescent wavelength when their fluorogenic scaffolds are sandwiched between the biosensor protein and target protein.

Moss project takes step toward first artificial plant genome

Good news! Amazing stuff!

"Researchers have crafted synthetic genomes for several types of bacteria, and an 18-year-long project to do the same for brewer’s yeast is close to completion. Now, a group in China has tackled a multicellular organism, synthesizing part of the genome of a type of moss. ... could smooth the way for creating artificial genomes for other multicellular organisms—and for turning the moss into a factory for medicines and other products. ...
The results support the contentious view that transposons aren’t essential for multicellular eukaryotes. ..."

From the abstract:

"Rapid advances in DNA synthesis techniques have enabled the assembly and engineering of viral and microbial genomes, presenting new opportunities for synthetic genomics in multicellular eukaryotic organisms. These organisms, characterized by larger genomes, abundant transposons and extensive epigenetic regulation, pose unique challenges. Here we report the in vivo assembly of chromosomal fragments in the moss Physcomitrium patens, producing phenotypically virtually wild-type lines in which one-third of the coding region of a chromosomal arm is replaced by redesigned, chemically synthesized fragments. By eliminating 55.8% of a 155 kb endogenous chromosomal region, we substantially simplified the genome without discernible phenotypic effects, implying that many transposable elements may minimally impact growth. We also introduced other sequence modifications, such as PCRTag incorporation, gene locus swapping and stop codon substitution. Despite these substantial changes, the complex epigenetic landscape was normally established, albeit with some three-dimensional conformation alterations. The synthesis of a partial multicellular eukaryotic chromosome arm lays the foundation for the synthetic moss genome project (SynMoss) and paves the way for genome synthesis in multicellular organisms."

Moss project takes step toward first artificial plant genome | Science | AAAS

A designer synthetic chromosome fragment functions in moss (no public access)

Earthmoss

Synthetic biology breakthrough fixes CO2 from the air better than nature by two orders of magnitude by using modified bacteria

Human ingenuity can easily handle the recycling of CO2 from the atmosphere at any volume if needed! Thus, this is one more reason why Global Warming is a hoax and Climate Change is a religion! Don't believe the propaganda and demagoguery!

"Scientists at the Max Planck Institute have developed a synthetic pathway that can capture CO2 from the air more efficiently than in nature, and shown how to implement it into living bacteria. The technique could help make biofuels and other products in a sustainable way. ..."

"Synthetic biology offers the opportunity to build biochemical pathways for the capture and conversion of carbon dioxide (CO2). Researchers ... have developed a synthetic biochemical cycle that directly converts CO2 into the central building block Acetyl-CoA. The researchers were able to implement each of the three cycle modules in the bacterium E.coli, which represents a major step towards realizing synthetic CO2 fixing pathways within the context of living cells."

From the abstract:

"Synthetic biology offers the opportunity to build solutions for improved capture and conversion of carbon dioxide (CO2) that outcompete those evolved by nature. Here we demonstrate the design and construction of a new-to-nature CO2-fixation pathway, the reductive tricarboxylic acid branch/4-hydroxybutyryl-CoA/ethylmalonyl-CoA/acetyl-CoA (THETA) cycle. The THETA cycle encompasses 17 enzymes from 9 organisms and revolves around two of the most efficient CO2-fixing enzymes described in nature, crotonyl-CoA carboxylase/reductase and phosphoenolpyruvate carboxylase. Here using rational and machine learning-guided optimization approaches, we improved the yield of the cycle by two orders of magnitude and demonstrated the formation of different biochemical building blocks directly from CO2. Furthermore, we separated the THETA cycle into three modules that we successfully implemented in vivo by exploiting the natural plasticity of Escherichia coli metabolism. Growth-based selection and/or 13C-labelling confirmed the activity of three different modules, demonstrating the first step towards realizing highly orthogonal and complex CO2-fixation pathways in the background of living cells."

Synthetic biology breakthrough fixes CO2 from the air better than nature

First step towards synthetic CO2 fixation in living cells Three modules forming a new-to-nature CO2 fixation cycle successfully implemented in E.coli

Construction and modular implementation of the THETA cycle for synthetic CO2 fixation (open access)

Fig. 1: The THETA cycle and its realization

Researchers created artificial enzymes programmed to target the genetic code of SARS-CoV-2 or cancer and destroy the virus or cancer

Amazing stuff! Sounds very promising!

"... Although most enzymes are proteins, some of these crucial reactions are catalysed by RNA, a chemical cousin of DNA, which can fold into enzymes known as ribozymes. Some classes of ribozyme are able to target specific sequences in other RNA molecules and cut them precisely.

In 2014, ... discovered that artificial genetic material known as XNA – in other words, synthetic chemical alternatives to RNA and DNA not found in nature – could be used to create the world’s first fully-artificial enzymes ... named XNAzymes.

At the beginning, XNAzymes were inefficient, requiring unrealistic laboratory conditions to function. Earlier this year, however, ... a new generation of XNAzymes, engineered to be much more stable and efficient under conditions inside cells. These artificial enzymes can cut long, complex RNA molecules and are so precise that if the target sequence differs by just a single nucleotide (the basic structural unit of RNA), they will recognise not to cut it. This means they can be programmed to attack mutated RNAs involved in cancer or other diseases, leaving normal RNA molecules well alone. ...

Now, in research ... report how they have used this technology to successfully ‘kill’ live SARS-CoV-2 virus. ... 

“Put simply, XNAzymes are molecular scissors which recognise a particular sequence in the RNA, then chop it up. As soon as scientists published the RNA sequence of SARS-CoV-2, we started scanning through looking for sequences for our XNAzymes to attack.”

While these artificial enzymes can be programmed to recognise specific RNA sequences, the catalytic core of the XNAzyme – the machinery that operates the ‘scissors’ – does not change. This means that creating new XNAzymes can be done in far less time than it normally takes to develop antiviral drugs. ...
“It’s worth remembering, however, that the amazingly successful Pfizer and Moderna COVID-19 vaccines are themselves based on synthetic RNA molecules – so it’s a really exciting and rapidly developing field, with enormous potential.” ..."

From the abstract:

"The unprecedented emergence and spread of SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, underscores the need for diagnostic and therapeutic technologies that can be rapidly tailored to novel threats. Here, we show that site-specific RNA endonuclease XNAzymes – artificial catalysts composed of single-stranded synthetic xeno-nucleic acid oligonucleotides (in this case 2’-deoxy-2’-fluoro-β-D-arabino nucleic acid) – may be designed, synthesised and screened within days, enabling the discovery of a range of enzymes targeting SARS-CoV-2 ORF1ab, ORF7b, spike- and nucleocapsid-encoding RNA. Three of these are further engineered to self-assemble into a catalytic nanostructure with enhanced biostability. This XNA nanostructure is capable of cleaving genomic SARS-CoV-2 RNA under physiological conditions, and when transfected into cells inhibits infection with authentic SARS-CoV-2 virus by RNA knockdown. These results demonstrate the potential of XNAzymes to provide a platform for the rapid generation of antiviral reagents."

‘Programmable molecular scissors’ could help fight COVID-19 infection | University of Cambridge Cambridge scientists have used synthetic biology to create artificial enzymes programmed to target the genetic code of SARS-CoV-2 and destroy the virus, an approach that could be used to develop a new generation of antiviral drugs.

XNAzymes targeting the SARS-CoV-2 genome inhibit viral infection (open access)

Fig. 1: RNA endonuclease XNAzymes retargeted to the SARS-CoV-2 genome.

This DNA Factory Is Aiming to Reprogram the World

Recommendable! This is about Gingko biloba ahm  Ginkgo Bioworks! And Mofif Foodworks ... Artificial meet, restoring lost perfumes from extinct plants etc. However, this representative of Gingko Bioworks is awful!

Animal tests reveal synthetic decoy protein protects against coronavirus

Good news! This sounds like a very elegant solution! If this new remedy is effective in vivo as well, this could be a breakthrough to find a cure for other virus infections as well!

"... Combining de novo design and directed evolution, they created a protein that binds to Sars-CoV-2 spike protein, blocking its infection pathway. The protein neutralises the virus in vitro and shows promising results in hamsters, protecting them from coronavirus infection after a small intranasal dose. ..."

Animal tests reveal synthetic decoy protein protects against coronavirus | Research | Chemistry World (behind paywall) Protein designed from scratch binds Sars-CoV-2 with high affinity and specificity

Cyber-spinach turns CO2 into sugar

Great news! This is the second blog post (see here) in less than two weeks about synthetic chloroplasts converting CO2 into useful chemical compounds!

Global Warming (aka climate change) is a hoax!





Cyber-spinach turns sunlight into sugar Combination of biological membrane and artificial chemistry could power future synthetic organisms.

Artificial chloroplasts turn sunlight and carbon dioxide into organic compounds

Global Warming (aka as Climate Change) is a hoax! Nothing beats human ingenuity! This process is probably a bit slow and inefficient, but it is only a matter of time and effort to fix that!

This is what I call recycling!

"Photosynthesis is a two-step process. In chloroplasts, chlorophyll molecules absorb sunlight and pass the extra energy to molecular partners that use it to generate the energy-storing chemicals adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH). A suite of other enzymes working in a complex cycle then use ATP and NADPH to convert CO2 from the air into glucose and other energy-rich organic molecules that the plant uses to grow."

Artificial chloroplasts turn sunlight and carbon dioxide into organic compounds | Science | AAAS

Building Synthetic Cells From Scratch

Posted: 1/5/2019

Trigger

Just read this long, fascinating, and in depth article How biologists are creating life-like cells from scratch Built from the bottom up, synthetic cells and other creations are starting to come together and could soon test the boundaries of life. published by Nature Journal on 11/7/2018

To build synthetic cells from the bottom up has been one of the hot frontiers in science for about the past two decades!

European Advances

Surprise, surprise European scientists appear to be at the cutting edge in this field. “In September [of 2018], the US National Science Foundation (NSF) announced its first programme on synthetic cells, funded to the tune of $10 million.” What a late comer to the game! Whereas “... several European investigators ... have proposed building a synthetic cell as one of the European Commission’s Future and Emerging Technologies Flagship schemes, which receive funding of €1 billion.”

Within A Decade

Some scientists predict that we will have functioning synthetic cells created from molecules or other basic ingredients within a decade. We may even achieve industrial scale by then.

Artificial Mitochondria

Without energy synthetic cells would not work very well. “Joachim Spatz’s group at the Max Planck Institute for Medical Research in Heidelberg, Germany, has built a rudimentary mitochondrion that can create ATP inside a vesicle.” In order to do this, they used latest microfluidic technologies.

More Efficient Photosynthesis

According to this article, scientists are already working replicating photosynthesis. Photosynthesis could be an energy source of the future.

“Another Max Planck [Institute for Terrestrial Microbiology] synthetic-biology group ... has been chipping away at other approaches to constructing cellular metabolic pathways. ... pathways that allow photosynthetic microbes to pull carbon dioxide from the environment and make sugars and other cellular building blocks. ...

His group sketched out a system design that could convert CO2 into malate, a key metabolite produced during photosynthesis. ... team searched databases for enzymes that might perform each of the reactions. For a few, they needed to tweak existing enzymes into designer ones.

In the end, they found 17 enzymes from 9 different organisms, including E. coli, an archaeon, the plant Arabidopsis and humans. The reaction, perhaps unsurprisingly, was inefficient and slow7. ... After some further enzyme engineering, … operates 20% more efficiently than photosynthesis. Expanding this work, [team] has begun constructing a crude version of a synthetic chloroplast ...”

As an aside: About four years ago it was shown that quantum mechanics explains the efficiency of photosynthesis (see e.g. here). How will this research of synthetic photosynthesis and quantum effects work out?

Programmable Bioreactors

“... at the University of Minnesota in Minneapolis is working on ways to build programmable bioreactors, by introducing simple genetic circuits into liposomes and fusing them together to create more-complex bioreactors. ...

builds these bioreactors using a spinning tube system ... which produces smaller liposomes. The researchers add circles of DNA called plasmids that they have designed to perform a particular function, along with all the machinery needed to make proteins from DNA.”

Minimal Genome

The J. Craig Vintner Institute (JCVI) “... took one of the smallest-known microbial genomes on the planet, that of the bacterium Mycoplasma mycoides, and systematically disrupted its genes to identify the essential ones. Once they had that information, they chemically stitched together a minimal genome in the laboratory.

This synthesized genome contained 473 genes — about half of what was in the original organism — and it was transplanted into a related bacterial species, Mycoplasma capricolum. In 2016, the team showed that this minimal synthetic genome could ‘boot up’ a free-living, although slow-growing organism … As a next step, and supported by an NSF grant of nearly $1 million, ... will attempt to install the JCVI-syn3.0a genome into a synthetic liposome containing the machinery needed to convert DNA into protein, to see whether it can survive. … JCVI has been doing adaptive laboratory evolution experiments with JCVI-syn3.0a, selecting for organisms that grow faster in a nutrient-rich broth. So far, after about 400 divisions, ... have obtained cells that grow about 15% faster than the original organism. ... a handful of gene-sequence changes popping up. But there’s no evidence yet of the microbe developing new cellular functions or increasing its fitness by leaps and bounds.”

The Amazing Bacterial Immune System

Posted: 2/4/2018

Trigger

Just read Bacterial Immune Systems Take the Stage A systematic study uncovering multiple new and unusual bacterial immune defense mechanisms could pave the way toward new biotech tools

“Until a decade ago, scientists were not aware that bacteria had complex immune systems – ones that could keep up with the pace of evolution in viruses called phages that infect bacteria.”

If confirmed, this is a huge discovery! We may now learn so much more about the origins and evolution of our own immune system and so much more.

At Least 11 Different Immune System Defense Mechanisms

This is absolutely mind boggling! Besides, the recently discovered and now widely employed gene editing method CRISPR, researchers at the Weizmann Institute of Science have discovered 10 more different immune system defense mechanisms in bacteria previously unknown.

The scope and breadth of study itself is absolutely mind boggling.