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Agriculture and Food

Sustainable Chemical Production through Microbial Cell Factories

In silico analysis of five industrial microorganisms identifies optimal strains and metabolic engineering strategies for producing 235 valuable chemicals.

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The global need for sustainable chemical production has become increasingly important due to climate change and the depletion of fossil fuels. In response to this environmental challenge, microbial cell factories are gaining attention as eco-friendly platforms for producing chemicals using renewable resources. To maximize production efficiency, metabolic engineering technologies have become crucial tools. However, difficulties in selecting suitable microbial strains and optimizing complex metabolic pathways continue to pose significant obstacles to practical industrial applications.

Researchers from KAIST’s Department of Chemical and Biomolecular Engineering have made a groundbreaking discovery by comprehensively evaluating the production capabilities of various industrial microbial cell factories using in silico simulations. This approach has enabled the identification of the most suitable microbial strains for producing specific chemicals, as well as optimal metabolic engineering strategies.

In the past, researchers attempted to determine the best strains and efficient metabolic engineering strategies through extensive biological experiments and meticulous verification processes. However, this approach required substantial time and costs. The introduction of genome-scale metabolic models (GEMs) has enabled systematic analysis of metabolic fluxes via computer simulations, revolutionizing both strain selection and metabolic pathway design.

Professor Lee’s team evaluated the production capabilities of five representative industrial microorganisms – E. coli, S. cerevisiae, B. subtilis, C. glutamicum, and P. putida – for 235 bio-based chemicals. Using GEMs, they calculated both the maximum theoretical yields and the maximum achievable yields under industrial conditions for each chemical. The team specifically proposed strategies such as introducing heterologous enzyme reactions derived from other organisms and exchanging cofactors used by microbes to expand metabolic pathways.

These strategies were shown to increase yields beyond the innate metabolic capacities of the microorganisms, resulting in higher production of industrially important chemicals such as mevalonic acid, propanol, fatty acids, and isoprenoids. Moreover, the team suggested strategies for improving microbial strains to maximize the production of various chemicals by analyzing metabolic fluxes in silico.

The researchers quantitatively identified the relationships between specific enzyme reactions and target chemical production, as well as the relationships between enzymes and metabolites, determining which enzyme reactions should be up- or down-regulated. Through this, the team presented strategies not only to achieve high theoretical yields but also to maximize actual production capacities.

Dr. Gi Bae Kim, the first author of this paper from the KAIST BioProcess Engineering Research Center, explained that by introducing metabolic pathways derived from other organisms and exchanging cofactors, it is possible to design new microbial cell factories that surpass existing limitations. The strategies presented in this study will play a pivotal role in making microbial-based production processes more economical and efficient.

In conclusion, this research serves as a key resource in the field of systems metabolic engineering, reducing difficulties in strain selection and pathway design, and enabling more efficient development of microbial cell factories. This technology is expected to greatly contribute to the future development of technologies for producing various eco-friendly chemicals, such as biofuels, bioplastics, and functional food materials.

Agriculture and Food

Unearthing Life’s Secrets: Deep Microbes Thrive without Sunlight

Chinese scientists uncovered a powerful energy source for deep Earth microbes: hydrogen and oxidants generated by rock fracturing during earthquakes. The process may also suggest how life could exist on other planets without sunlight.

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The discovery that life can exist and even flourish in environments devoid of sunlight has long been a topic of fascination for scientists. A recent study published in Science Advances by Chinese researchers has shed new light on this phenomenon, revealing how microbes in deep subsurface areas derive energy from chemical reactions driven by crustal faulting. This groundbreaking research challenges the conventional wisdom that “all life depends on sunlight” and offers critical insights into the existence of life deep below Earth’s surface.

Led by Professors Hongping He and Jianxi Zhu from the Guangzhou Institute of Geochemistry, a team of researchers simulated crustal faulting activities to understand how free radicals produced during rock fracturing can decompose water, generating hydrogen and oxidants like hydrogen peroxide. These substances create a distinct redox gradient within fracture systems, which can further react with iron in groundwater and rocks – oxidizing ferrous iron (Fe²⁺) to ferric iron (Fe³⁺) or reducing ferric iron (Fe³⁺) to ferrous iron (Fe²⁺), depending on local redox conditions.

In microbe-rich fractures, the researchers found that hydrogen production driven by earthquake-related faulting was up to 100,000 times greater than that from other known pathways, such as serpentinization and radiolysis. This process effectively drives iron’s redox cycle, influencing geochemical processes of elements like carbon, nitrogen, and sulfur – sustaining microbial metabolism in the deep biosphere.

This study has far-reaching implications for our understanding of life on Earth and beyond. Professors He and Zhu note that fracture systems on other Earth-like planets could potentially provide habitable conditions for extraterrestrial life, offering a new avenue for the search for life beyond Earth. The research was financially supported by various sources, including the National Science Fund for Distinguished Young Scholars and the Strategic Priority Research Program of CAS.

In conclusion, this groundbreaking study has challenged our understanding of life’s dependence on sunlight and revealed a previously unknown source of energy for microbes in deep subsurface areas. As we continue to explore the mysteries of the deep biosphere, we may uncover even more secrets that will rewrite the textbooks on life on Earth and beyond.

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Agriculture and Food

Breaking New Ground: Scientists Develop Groundbreaking Chromosome Editing Technology

A group of Chinese scientists has created powerful new tools that allow them to edit large chunks of DNA with incredible accuracy—and without leaving any trace. Using a mix of advanced protein design, AI, and clever genetic tweaks, they’ve overcome major limitations in older gene editing methods. These tools can flip, remove, or insert massive pieces of genetic code in both plants and animals. To prove it works, they engineered rice that’s resistant to herbicides by flipping a huge section of its DNA—something that was nearly impossible before.

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The field of genetic engineering has taken a significant leap forward with the development of two new genome editing technologies by a team of Chinese researchers led by Prof. Gao Caixia from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences. These innovations, collectively known as Programmable Chromosome Engineering (PCE) systems, have been published in the prestigious journal Cell.

The PCE system is an upgrade to the well-known Cre-Lox technology, which has long been used for precise chromosomal manipulation. However, this older method had three major limitations that hindered its broader application: low recombination efficiency, reversible recombination activity, and the need for a scar (a small DNA fragment) at the editing site.

The research team tackled each of these challenges by developing novel methods to advance the state of this technology. Firstly, they created a high-throughput platform for rapid recombination site modification and proposed an asymmetric Lox site design that reduces reversible recombination activity by over 10-fold.

Secondly, they utilized their recently developed AiCE model – a protein-directed evolution system integrating general inverse folding models with structural and evolutionary constraints – to develop AiCErec. This approach enabled precise optimization of Cre’s multimerization interface, resulting in an engineered variant with a recombination efficiency 3.5 times that of the wild-type Cre.

Lastly, they designed and refined a scarless editing strategy for recombinases by harnessing the high editing efficiency of prime editors to develop Re-pegRNA, a method that uses specifically designed pegRNAs to perform re-prime editing on residual Lox sites, precisely replacing them with the original genomic sequence.

The integration of these three innovations led to the creation of two programmable platforms, PCE and RePCE. These platforms allow flexible programming of insertion positions and orientations for different Lox sites, enabling precise, scarless manipulation of DNA fragments ranging from kilobase to megabase scale in both plant and animal cells.

Key achievements include targeted integration of large DNA fragments up to 18.8 kb, complete replacement of 5-kb DNA sequences, chromosomal inversions spanning 12 Mb, chromosomal deletions of 4 Mb, and whole-chromosome translocations. As a proof of concept, the researchers used this technology to create herbicide-resistant rice germplasm with a 315-kb precise inversion.

This groundbreaking work not only overcomes the historical limitations of the Cre-Lox system but also opens new avenues for precise genome engineering in various organisms, demonstrating its transformative potential for genetic engineering and crop improvement.

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Agriculture and Food

The Ancient Origins of Potatoes Revealed

About 9 million years ago, a wild interspecies fling between tomato-like plants and potato relatives in South America gave rise to one of the world’s most important crops: the potato. Scientists have now traced its roots to a rare natural hybridization that created the tuber, a storage organ that allowed the plant to survive harsh Andean environments and spread rapidly.

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The mystery of where potatoes came from has been solved by an international research team. Scientists have uncovered that 9 million years ago, a natural interbreeding event occurred between tomato plants and potato-like species from South America, giving rise to the modern-day potato. This ancient evolutionary event triggered the formation of the tuber, the enlarged underground structure that stores nutrients in plants like potatoes, yams, and taros.

The research team analyzed 450 genomes from cultivated potatoes and 56 wild potato species to solve this long-standing mystery. They found that every potato species contained a stable mix of genetic material from both Etuberosum and tomato plants, suggesting an ancient hybridization between the two. The team also traced the origins of the potato’s key tuber-forming genes, which are a combination of genetic material from each parent.

The discovery reveals how a hybridization event can spark the evolution of new traits, allowing even more species to emerge. This is particularly significant in the context of one of the world’s most important crops, the potato. As one of the world’s most widely cultivated foods, potatoes have long puzzled scientists with their seemingly identical appearance to Etuberosum plants but lack of tubers.

To fill this knowledge gap, researchers analyzed 450 genomes from cultivated potatoes and 56 wild potato species. They found that every potato species contained a stable mix of genetic material from both Etuberosum and tomato plants. This suggests an ancient hybridization event occurred between the two, which gave rise to the modern-day potato.

The team’s findings also reveal how this ancient evolutionary innovation coincided with the rapid uplift of the Andes mountains. As new ecological environments emerged, early potatoes were able to quickly adapt and survive in harsh weather conditions using their tubers as a nutrient storage system. This allowed them to rapidly expand and fill diverse ecological niches from mild grasslands to high and cold alpine meadows in Central and South America.

The discovery of the potato’s ancient origins is a significant breakthrough in understanding how new species emerge. It highlights the importance of natural interbreeding events in shaping the evolution of plants and their adaptation to changing environments.

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