Design, Synthesis, and Biological Evaluation of Isoform-Selective Akt3 Degraders.

Akt3, a serine/threonine kinase within the PI3K-Akt-mTOR signaling pathway, is overactivated in various cancers, making it a promising therapeutic target. The research aimed to create compounds that selectively degrade Akt3, sparing Akt1 and Akt2, to enhance the clinical benefits. A series of compounds with different linkers and E3 ligands were synthesized and evaluated for their degradation potencies and selectivity.

Advances in Metabolic Engineering of Microbial Cell Factories for the Biosynthesis of l-Serine.

l-Serine, a nonessential amino acid in humans, possesses significant physiological functions and is widely used in the food, cosmetic, and pharmaceutical industries. Driven by steadily growing market demand and promising prospects, increasing attention has focused on the sustainable, biobased production of l-serine via low-carbon microbial synthesis, facilitated by advances in biotechnology. Significant progress has been made in the metabolic engineering of microbial cell factories for the biosynthesis of l-serine.

Biotechnological production of healthful conjugated fatty acids.

Conjugated fatty acids (CFAs) are important for human health. They are traditionally obtained by extraction or chemical synthesis, but can alternatively be produced using biotechnology. Current efforts are aimed at improving the biotransformation process and capability for de novo biosynthesis.

Recent advances and multiple strategies for the synthesis of terpenoid fragrances and flavors in model microorganisms.

Terpenoids, known for their structural and functional diversity, play a significant role in various fields such as energy, cosmetics, pharmaceuticals, and fragrances. With the increasing globalization of the fragrance and flavor market, there is an urgent need to develop microbial cell factories to sustainably produce terpenoids through fermentation using renewable raw materials. With advancements in biotechnology, constructing efficient microbial cell factories for the heterologous synthesis of terpenoids to meet production demands has become feasible.

Biosynthesis of conjugated linoleic acid: current status and future perspectives.

Conjugated linoleic acid (CLA) has received much attention for its beneficial physiological effects, particularly anticancer and metabolic control activity. However, traditional sources rely on extraction and chemical synthesis, both of which are not commercially viable. This article describes the research progress on sustainable alternative biosynthesis methods for the production of CLA, which is an attractive approach for commercial production because of its high stereoselectivity and convenient purification process.

Biosynthesis of 5-hydroxymethyl-2-furancarboxylic acid from 5-hydroxymethylfurfural new whole-cell biocatalysts.

The selective oxidation of biomass-derived 5-hydroxymethylfurfural (HMF) to value-added furan compounds presents significant challenges due to the inherent high reactivity of HMF. In this study, two microorganisms were identified as whole-cell biocatalysts for the synthesis of 5-hydroxymethylfuroic acid (HMFCA) from HMF. The cells of sp.

Early net ultrafiltration thresholds and mortality in critically ill patients with septic acute kidney injury receiving continuous renal replacement therapy.

Background: Net ultrafiltration (NUF) rates correlate with outcomes in critically ill patients on continuous renal replacement therapy (CRRT), but optimal strategies for septic acute kidney injury (AKI) are unclear. This study evaluated early NUF rates and survival in septic AKI.

Methods: A retrospective cohort of 219 adults with septic AKI requiring CRRT at a tertiary ICU was analyzed.

Enhancing Cordycepin Biosynthesis in via Lipid Droplets Compartmentalization Engineering and Optimized Fermentation Strategies.

Cordycepin, a physiologically active nucleoside compound with broad applications in healthcare, is biosynthesized in through a protein complex formed by CmCns1 and CmCns2. To enhance cordycepin heterologous production in , this study confirmed the colocalization of CmCns1 and CmCns2 on lipid droplets, with CmCns1 dominating this process by recruiting CmCns2 from the cytoplasm to lipid droplets via strong interactions. Critical lipid-droplet-targeting motifs within CmCns1 were identified.

Engineering strategies for producing medium-long chain dicarboxylic acids in oleaginous yeasts.

Medium-long chain dicarboxylic acids (DCAs, C ≥ 6) are essential chemical raw materials, with wide applications in the chemical, pharmaceutical, material and food industries. However, the traditional chemical synthesis methods cause environmental pollution and are not in line with goals of sustainable development. With the development of synthetic biology, high-value-added DCAs can be biosynthesized from hydrophobic substrates (HSs) using suitable microorganisms.

Advances in synthesizing plant-derived isoflavones and their precursors with multiple pharmacological activities using engineered yeasts.

Isoflavones such as daidzein and genistein are naturally occurring compounds found in plants such as legumes. They have diverse pharmacological activities, making them valuable in the food, pharmaceutical, and cosmetic industries. Currently, isoflavones are mainly obtained through the extraction of plant biomass.

Biotechnological Production of Carotenoids Using .

Carotenoids are a group of tetraterpenoid natural products with a variety of physiological activities, which led to their application in food, cosmetics, agriculture, and other industries with broad market prospects. The fermentation of carotenoids using engineered microbial hosts has emerged as an efficient, sustainable, and environmentally friendly production method with significant potential for further development. (), an unconventional oleaginous yeast, has intrinsic advantages as a host strain for the production of carotenoids.

Enhancing Precursor Supply and Engineering Efflux Systems to Improve Abscisic Acid Production and Secretion in .

Abscisic acid is a sesquiterpene phytohormone with extensive applications in agriculture and human health. Currently, it is produced through fermentation of , a plant pathogenic filamentous fungus. The process requires morphology controls, which complicates production and strain optimization.

Dynamic regulation combined with systematic metabolic engineering for high-level palmitoleic acid accumulation in oleaginous yeast.

Palmitoleic acid (POA, C16:1Δ) is widely recognized for its preventive and therapeutic effects in various chronic and cardiovascular diseases, but the current production practices based on plant extraction are both economically and ecologically unsustainable. Although Yarrowia lipolytica is capable of producing POA, it only accumulates to a small percentage of total fatty acids. The present study aimed to enhance the accumulation of POA by employing a two-layer engineering strategy, encompassing the modulation of the fatty acid profile and the promotion of the accumulation of POA-rich lipids.

Biocatalytic Hydrogenation of Biomass-Derived Furan Aldehydes to Alcohols.

The biomass-derived furan aldehydes furfural (FF) and 5-hydroxymethylfurfural (HMF) are versatile platform chemicals used to produce various value-added chemicals through further valorization processes. Selectively reducing C═O in FF and HMF molecules to form furfuryl alcohol (FAL) and 2,5-bis(hydroxymethyl)furan (BHMF), represents an important research field in upgrading biomass-based furan compounds. Currently, the reduction of furan aldehydes to furan alcohols through chemical transformation often leads to unavoidable environmental issues and the formation of potential byproducts.

Advancing Succinic Acid Biomanufacturing Using the Nonconventional Yeast .

Succinic acid is an essential bulk chemical with wide-ranging applications in materials, food, and pharmaceuticals. With the advancement of biotechnology, there has been a surge in focus on low-carbon sustainable microbial synthesis methods for producing biobased succinic acid. Due to its high intrinsic acid tolerance, has gained recognition as a competitive chassis for the industrial manufacture of succinic acid.

Systematic metabolic engineering of for efficient production of phytohormone abscisic acid.

Abscisic acid (ABA) is an important phytohormone with diverse applications. It currently relies on the fermentation of , which suffers from limited availability of genetic engineering tools. Here, was engineered to enable biosynthesis of ABA.

Engineering for Efficient Synthesis of Geranylgeraniol.

Geranylgeraniol (GGOH) is a crucial component in fragrances and essential oils, and a valuable precursor of vitamin E. It is primarily extracted from the oleoresin of , but is challenged by long plant growth cycles, severe environmental pollution, and low extraction efficiency. Chemically synthesized GGOH typically comprises a mix of isomers, making the separation process both challenging and costly.

Engineering Yarrowia lipolytica for sustainable Cis-13, 16-docosadienoic acid production.

Cis-13, 16-docosadienoic acid (DDA) is an omega-6 polyunsaturated fatty acid with great potential for application in medicine and health. Using microbial cell factories for DDA production is considered a viable alternative to extracting DDA from plant seeds. In this study, using Yarrowia lipolytica Po1f (Δku70) as a chassis, firstly, the adaptation of three elongases in Po1f (Δku70) were explored.

Harnessing oleaginous yeast to produce omega fatty acids.

Omega fatty acids are important for human health. They are traditionally extracted from animals or plants but can be alternatively produced using oleaginous yeast. Current efforts are producing yeast strains with similar fatty acid distributions and powerful lipogenesis capacity.

Exploiting synthetic biology platforms for enhanced biosynthesis of natural products in Yarrowia lipolytica.

With the rapid development of synthetic biology, researchers can design, modify, or even synthesize microorganisms de novo, and microorganisms endowed with unnatural functions can be considered "artificial life" and facilitate the development of functional products. Based on this concept, researchers can solve critical problems related to the insufficient supply of natural products, such as low yields, long production cycles, and cumbersome procedures. Due to its superior performance and unique physiological and biochemical characteristics, Yarrowia lipolytica is a favorable chassis cell used for green biomanufacturing by numerous researchers.

Engineering for Sustainable Production of the Pomegranate Seed Oil-Derived Punicic Acid.

Punicic acid is a conjugated linolenic acid with various biological activities including antiobesity, antioxidant, anticancer, and anti-inflammatory effects. It is often used as a nutraceutical, dietary additive, and animal feed. Currently, punicic acid is primarily extracted from pomegranate seed oil, but it is restricted due to the extended growth cycle, climatic limitations, and low recovery level.

Building Cell Factories for Advanced Biomanufacturing: Challenges and Solutions.

Microbial cell factories have shown great potential for industrial production with the benefit of being environmentally friendly and sustainable. is a promising and superior non-model host for biomanufacturing due to its cumulated advantages compared to model microorganisms, such as high fluxes of metabolic precursors (acetyl-CoA and malonyl-CoA) and its naturally hydrophobic microenvironment. However, although diverse compounds have been synthesized in cell factories, most of the relevant studies have not reached the level of industrialization and commercialization due to a number of remaining challenges, including unbalanced metabolic flux, conflict between cell growth and product synthesis, and cytotoxic effects.