(Press-News.org)
Terpenoids, the largest family of natural products, have gained significant attention for their diverse applications in industries such as pharmaceuticals, fragrances, and biofuels. However, the efficient synthesis of terpenoids using engineered cell factories has been hindered by the limited supply of isoprene pyrophosphate (IPP), the key building block for terpenoid production. Now, a research team led by Jian Chen at Jiangnan University in China has made a groundbreaking discovery that could revolutionize terpenoid bioproduction.
In their research article published in the journal Engineering, Chen and his team unveil a novel approach to address the challenge of insufficient IPP supply. By investigating the metabolic flux distribution in Bacillus subtilis (B. subtilis), the researchers identified an imbalance between central metabolism and IPP production as a major bottleneck. To overcome this hurdle, they devised a strategy to remodel the IPP metabolism using genetically encoded two-input–multi-output (TIMO) circuits.
The TIMO circuits, which respond to pyruvate and malonyl-CoA, were engineered to fine-tune the metabolic flux towards IPP synthesis. This remodeling approach resulted in a remarkable increase in the IPP pool, up to four folds higher than the original levels. To validate the effectiveness of their technique, the researchers applied the TIMO circuits to enhance the production of three valuable terpenoids: menaquinone-7 (MK-7), lycopene, and β-carotene.
The results were astounding. The titer of MK-7, a terpenoid used in the prevention of osteoporosis, arterial calcification, and Parkinson’s disease, reached an unprecedented 1549.6 mg/L in a 50 L bioreactor. This achievement represents the highest reported titer of MK-7 to date. Additionally, lycopene production was boosted nine folds, and β-carotene production increased by 0.9 folds.
“This research breakthrough opens up new possibilities for the efficient bioproduction of terpenoids,” said Shasha Zhao, the editor of Engineering. “The TIMO genetic circuit-assisted IPP metabolism remodeling framework provides a powerful tool for fine-tuning complex metabolic pathways. It has the potential to revolutionize the production of a wide range of valuable chemicals.”
The success of this study not only demonstrates the potential of the TIMO circuits for the production of terpenoids, but also highlights their versatility and robustness. The researchers believe that this regulatory system can be applied to other chassis cells, offering an alternative strategy for remodeling IPP metabolism.
The implications of this research extend beyond terpenoid production. The multi-signal, coordinated, and cascaded dynamic regulation strategies employed in this study lay the foundation for the rational and global fine-tuning of complex metabolic pathways. This breakthrough could pave the way for the production of various other chemicals, driving advancements in multiple industries.
As the world continues to seek sustainable and eco-friendly alternatives to traditional chemical synthesis, this research presents a promising avenue for the development of bioproduction processes that are both economically viable and environmentally friendly.
The paper “Remodeling Isoprene Pyrophosphate Metabolism for Promoting Terpenoids Bioproduction”, authored by Xianhao Xu, Xueqin Lv, Shixiu Cui, Yanfeng Liu, Hongzhi Xia, Jianghua Li, Guocheng Du, Zhaofeng Li, Rodrigo Ledesma-Amaro, Jian Chen, Long Liu. Full text of the open access paper: https://doi.org/10.1016/j.eng.2023.03.019. For more information about the Engineering, follow us on Twitter (https://twitter.com/EngineeringJrnl) & like us on Facebook (https://www.facebook.com/EngineeringPortfolio).
About Engineering
Engineering (ISSN: 2095-8099 IF:12.8) is an international open-access journal that was launched by the Chinese Academy of Engineering (CAE) in 2015. Its aims are to provide a high-level platform where cutting-edge advancements in engineering R&D, current major research outputs, and key achievements can be disseminated and shared; to report progress in engineering science, discuss hot topics, areas of interest, challenges, and prospects in engineering development, and consider human and environmental well-being and ethics in engineering; to encourage engineering breakthroughs and innovations that are of profound economic and social importance, enabling them to reach advanced international standards and to become a new productive force, and thereby changing the world, benefiting humanity, and creating a better future.
END
Scientists at The University of Manchester are set to receive a multi-million-pound grant to advance our understanding of interactions in microbiomes and how they might impact the world around us.
The research, funded by the Biotechnology and Biological Sciences Research Council’s (BBSRC) strategic Longer and Larger (sLoLa) grants programme, takes the first major step towards understanding complex microbial communities and will support the move towards a more sustainable and Net Zero ...
Many of today’s medications belong to groups of relatively large molecules such as peptides. They are used to treat a wide range of diseases, including diabetes, obesity and prostate cancer. Unfortunately, taking these medications in tablet form is out of the question in most cases because they would break down in the digestive tract or remain too large to reach the bloodstream. Consequently, the patient’s only option is to receive their medication via injection.
A group of researchers at ETH Zurich have developed ...
Scientists have demonstrated the existence of gravity between antimatter and Earth, reaffirming Albert Einstein’s General Theory of Relativity.
It is thought that Isaac Newton's historic work on gravity was inspired by watching an apple fall to Earth from a tree. But for decades, scientists have wondered what would happen to an “anti-apple” made of antimatter - would it fall in the same way if it existed?
Until now, the question has left scientists with an incomplete picture of the Universe's gravitating content.
In a paper published today in Nature, the ALPHA collaboration at CERN’s Antimatter Factory, which ...
Augmented reality (AR) technology has long fascinated both the scientific community and the general public, remaining a staple of modern science fiction for decades.
In the pursuit of advanced AR assistants – ones that can guide people through intricate surgeries or everyday food preparation, for example – a research team from NYU Tandon School of Engineering has introduced Augmented Reality Guidance and User-Modeling System, or ARGUS.
An interactive visual analytics tool, ARGUS is engineered to support the development of intelligent AR assistants that can run on devices like Microsoft ...
Normal aging is usually associated with a decline in memory, although it is unclear what factors play a role. In a new study, researchers studied specific interneurons, which serve as communication centers that connect other neurons, in the regions of the brain that are important for learning and memory.
Increasing age places people at risk, whether it is because of a normal decrease in cognitive ability or due to postoperative cognitive disorders. In the latter, the deficits can persist for many months after surgery especially when the patients are older than 60. Unfortunately, the ...
A new study in JAMA Network Open may provide key answers to how to help people experiencing chronic back pain.
The study, published today, examined the critical connection between the brain and pain for treating chronic pain. Specifically, they looked at the importance of pain attributions, which are people’s beliefs about the underlying causes of their pain, to reduce chronic back pain severity.
“Millions of people are experiencing chronic pain and many haven’t found ways to help with the pain, making it clear that something is missing in the way we’re diagnosing and treating people,” said the ...
RICHLAND, Wash.—For decades, researchers have assumed that the inevitable filmy buildup on electrodes inside rechargeable batteries is the driver of performance loss. Now, we know that view is backward.
The buildup of mossy or tree-like structured lithium metal deposits on battery electrodes is not the root cause of performance loss, but rather a side effect. The first direct measurement of the electrical properties at the boundary between the solid electrode and the liquid electrolyte inside a rechargeable battery is reported today in Nature Energy.
The study, led by a research team at the Department of Energy’s Pacific Northwest National Laboratory, shows that the so-called ...
UCLA-led research suggests that diabetes control can significantly improve for Latinos when a pharmacist implements an intervention that addresses these patients’ barriers to medication adherence.
In this pharmacist-led intervention, pharmacists reviewed the patients’ lab results, vital signs, and barriers to adherence. They then used this information to design a personally-tailored intervention to boost medication adherence and optimize the treatment regimen.
The study is the first to evaluate a collaboration between pharmacist and physicians aimed at improving diabetes care in a large healthcare system among Latino patients, said study lead Dr. Kimberly Narain, ...
CAMBRIDGE, MA -- Alzheimer’s disease affects more than 6 million people in the United States, and there are very few FDA-approved treatments that can slow the progression of the disease.
In hopes of discovering new targets for potential Alzheimer’s treatments, MIT researchers have performed the broadest analysis yet of the genomic, epigenomic, and transcriptomic changes that occur in every cell type in the brains of Alzheimer’s patients.
Using more than 2 million cells from more than 400 postmortem brain samples, the researchers analyzed how gene expression is disrupted as Alzheimer’s progresses. They also tracked changes in ...
Key takeaways:
Scientists have developed “multielement ink” – the first “high-entropy” semiconductor that can be processed at low-temperature or room temperature.
Multielement ink could enable cost-effective and energy-efficient semiconductor manufacturing.
The new semiconducting material could accelerate the sustainable production of next-gen microelectronics, photovoltaics, solid state lighting, and display devices.
Semiconductors are the heart of almost every ...
