As efficient and sustainable proteins, single-cell proteins (SCPs) demonstrate significant potential in alleviating the constraints of traditional agricultural resources and reducing the carbon footprint of food manufacturing. Low-carbon C1/C2 feedstocks, such as carbon dioxide, methanol, and acetate, offer distinct advantages, including broad availability, low costs, and minimal carbon footprints. However, the assimilation of these feedstocks and the accumulation of proteins are still limited by key bottlenecks such as poor host cell adaptability, imbalanced metabolic flux distribution, and inefficient energy supply. In recent years, remarkable progress has been achieved in the discovery, evaluation, and rational engineering of host strains for the efficient bioconversion of C1/C2 feedstocks. The application of synthetic biology, metabolic engineering, and laboratory adaptive evolution has enabled the continuous improvements of the strain tolerance to C1/C2 feedstocks, assimilation efficiency, and intracellular protein accumulation capacity. On the basis of these advancements, various SCP production processes utilizing C1/C2 feedstocks are gradually advancing toward pilot-scale and industrial applications. This review systematically summarizes the strategies for constructing chassis cells that efficiently utilize C1/C2 feedstocks, key metabolic engineering technologies driving efficient SCP production, and the current technological and industrial status of SCP production from different C1/C2 feedstocks. Furthermore, it discusses challenges related to energy efficiency, nutritional quality, safety, and downstream scale-up, aiming to provide a theoretical foundation and technical reference for the sustainable development and industrial application of SCPs produced from C1/C2 feedstocks.

Against the dual constraints of shrinking carbon budgets and geopolitical rivalry for resource supplies, traditional manufacturing is confronted with various bottlenecks and needs to transform into a sustainable development mode imperatively. Microbial gas fermentation adopts feedstocks including industrial off-gas, gasification syngas, and natural gas to produce diversified products such as green biofuels, fine chemicals, and microbial proteins. With the advantages of high carbon utilization efficiency, mild reaction conditions, and environmental friendliness, it plays a vital role in carbon resource recycling and emission reduction of greenhouse gases. This paper systematically reviews the research and industrial progress in microbial gas fermentation. First, the performance and limitations of three generations of biomass feedstocks are analyzed and compared, and the technical advantages of microbial gas fermentation are illustrated. Secondly, the core metabolic pathways, growth preferences, and product synthesis characteristics of different gas-fermenting microorganisms are summarized. For commercial application, this study comprehensively sorts out the technical characteristics and limiting factors of industrial gas fermentation processes including feed gas pretreatment, gas-liquid mass transfer, multistage continuous fermentation, and in-situ product recovery, as well as their impacts on the fermentation process. Meanwhile, this work reviews global and domestic industrial cases, and elaborates on the characteristics of core microbial strains, typical technical routes, and product structures of various enterprises. In addition, in view of the technical shortcomings and further development needs of industrial gas fermentation, feasible strategies are proposed, mainly including strain performance improvement, fermentation equipment upgrading, intelligent process control, and improvement of economic benefits. This review aims to provide pivotal insights into the scaled-up and industrial application of microbial gas fermentation technology.

As an important branch of carbon capture, utilization, and storage (CCUS) technology, microbial carbon capture and utilization technology has become a vital bridge linking carbon neutrality and the sustainable bioeconomy. This paper systematically reviews the research progress in four technical pathways for converting CO₂ into starch, protein, microalgae biomass, and ethanol, and conducts carbon footprint and techno-economic analysis with ethanol as a typical case. The results indicate that the carbon reduction potential of microbial carbon capture and utilization technology depends on the supply mode of energy and value positioning of products. The in-depth integration of synthetic biology and electrocatalysis is reshaping the economic boundaries of carbon utilization. This study can provide references for technical pathway selection, research and development investment decision-making, and policy formulation.

L-threitol is a significant intermediate in pharmaceutical synthesis. Previously, we developed a one-pot, two-step multi-enzyme cascade for synthesizing L-threitol from formaldehyde. In this pathway, benzoylformate decarboxylase (BFD) and fructose-6-phosphate aldolase (FSA) catalyze the conversion of formaldehyde into L-erythrulose. This is followed by the reduction of L-erythrulose to L-threitol, driven by L-threitol dehydrogenase (TDH) and a methanol dehydrogenase (MDH)/isopropanol cofactor regeneration system. While this route boasts high atom economy and minimal by-products, the compatibility and optimal concentrations of the enzymes required optimization. [Objective] To systematically optimize the dosages and compatibility of enzymes in the multi-enzyme cascade to enhance both the reaction rate and conversion efficiency. [Methods] The activities of four key enzymes—BFD, FSA, TDH, and MDH—were assessed. Subsequently, factors including enzyme dosage, the cofactor regeneration system, reaction duration, and temperature were optimized step-by-step to improve the system compatibility. [Results] The optimal reaction conditions were determined as follows: enzyme dosages of BFD, FSA, TDH, and MDH being 10, 1, 1, and 8 mg/mL, respectively. Notably, the dosages of FSA and TDH were reduced by 87% and 67%, respectively, compared with pre-optimization levels. Other optimal parameters included a NAD⁺ concentration of 2 mmol/L, a reaction temperature of 30 ℃, and reaction duration of 8 h (representing a 60% decrease from that of the original system). Under these conditions, the maximum L-threitol concentration reached 166.76 mmol/L, with a yield of 89%. In a scale-up experiment, the L-threitol yield remained at 80%, representing a 43% increase compared with the pre-optimization level. [Conclusion] By systematically optimizing enzyme compatibility and reaction conditions, this study significantly reduces the enzyme dosages and reaction duration for converting formaldehyde to L-threitol. Simultaneously, it substantially improves the production efficiency and yield, establishing a robust foundation for the enzymatic synthesis of L-threitol from formaldehyde.

[Objective] 1,3-propanediol (PDO) is an important chemical monomer. Its biosynthetic routes mainly rely on carbon sources such as glycerol or glucose, which suffer from low carbon efficiency or reliance on food-based resources. Methanol, as a non-food renewable carbon source, offers advantages of a high reduction degree and low costs. However, the existing bioconversion of methanol to PDO is limited by low methanol utilization efficiency and cytotoxicity. [Methods] In this study, a novel route combining enzymatic and whole-cell catalysis for the conversion of methanol to PDO was designed. First, an in vitro multi-enzyme cascade system was used to convert methanol to glycerol, comprising alcohol oxidase (AOX), catalase (CAT), formaldehyde lyase (FLS), glycerol dehydrogenase (GldA), and formate dehydrogenase (FDH). After 4 h of reaction, the glycerol concentration reached 63.3 mmol/L, with a carbon conversion efficiency of 95.0% from methanol to glycerol. Second, the glycerol transporter GlpF, glycerol dehydratase DhaB123 and its activator GdrAB, and the NADPH-dependent aldehyde reductase YqhD were introduced into Corynebacterium glutamicum to construct a recombinant strain, enabling the whole-cell conversion of glycerol to PDO. Under optimized conditions, the carbon conversion efficiency from glycerol to PDO reached 96.0%. [Results] To convert methanol to PDO, we coupled the two processes, which achieved a final PDO titer of 30.4 mmol/L and the overall carbon conversion efficiency of 90.2% from methanol to PDO. [Conclusion] This study achieves efficient conversion of methanol to PDO and provides a new strategy for the green biomanufacturing of methanol-based high-value chemicals.

[Objective] To address the bottlenecks of heavy reliance on fossil resources and severe environmental pollution associated with chemical synthesis, circumvent the “competing with humans for food” dilemma of conventional sugar-based biorefineries, and contribute to the achievement of carbon neutrality. This study developed a low-carbon engineering strain that can directly capture one-carbon (C1) gases and synthesize high-value-added products via metabolic engineering, thereby realizing the sustainable and efficient biosynthesis of ethyl acetate (EA). [Methods] With the autotrophic microorganism Clostridium ljungdahlii, which possesses a natural carbon-fixing ability, as the expression chassis, the lipase B from Candida antarctica (CALB) exhibiting robust esterification activity was heterologously expressed, and thus a metabolic pathway for converting intracellular short-chain precursors (acetate and ethanol) into EA was constructed. To overcome the challenges of low cell density and misallocated precursor pools inherent in autotrophic carbon fixation, we systematically parsed and reshaped different trophic regimes for fermentation. The performance of the recombinant strain was evaluated across heterotrophic (fructose), autotrophic (CO/CO₂), and mixotrophic (fructose+CO/CO₂) regimes in terms of biomass accumulation, metabolic flux distribution, and target product synthesis. [Results] The foreign lipase CALB was successfully and functionally expressed inside the acetogenic chassis, effectively driving the precursor flux toward target ester synthesis. The engineered strain produced 16.49 mg/L of EA under heterotrophic conditions and 9.18 mg/L of EA under purely autotrophic conditions. Crucially, the dual-substrate mixotrophic fermentation regime not only bypassed the carbon catabolite repression (CCR) effect but also synergistically enhanced both cell growth and precursor supply. This approach boosted the ultimate EA titer to 36.25 mg/L, demonstrating superior catalytic efficiency and targeted esterification performance compared with single trophic modes. [Conclusion] The C. ljungdahlii strain engineeredthrough systematic metabolic modifications and fermentation mode remodeling can successfully capture and convert greenhouse gases/industrial off-gases into high-value-added ester products. This gas-fermenting cell factory represents a promising chassis for the production of high-value-added derivatives in the future, expanding the technical frontiers for low-carbon industrial blueprints driven by synthetic biology.

[Objective] To address the low yield and conversion rate in the biosynthesis of glycolic acid, we developed a whole-cell catalytic system with ethylene glycol as the substrate to obtain a strain with a high yield of glycolic acid and an efficient biosynthesis process. [Methods] With ethylene glycol as the substrate, wild-type strains were screened for their glycolic acid synthetic performance. The catalytic conditions of the optimal strain were systematically optimized to enhance the whole-cell catalytic efficiency in the production of glycolic acid. Ultraviolet mutagenesis combined with a glycolic acid biosensor-based high-throughput screening was employed to isolate high-yield strains, which were further validated in a 5-L fermenter. [Results] Pichia kudriavzevii GX-01 was successfully screened out, which could grow on glucose and produce glycolic acid from ethylene glycol via whole-cell catalysis. The whole-cell catalytic conditions were optimized by single-factor experiments as a catalytic temperature of 30 ℃, supplementation with 0.50 g MgCO₃ to adjust the system pH after 6 h of reaction, a loading volume of 50 mL in a 250-mL flask, an initial glucose concentration of 25 g/L, and an initial ethylene glycol concentration of 20 g/L. Under these conditions, the glycolic acid titer in shake flasks reached 19.30 g/L after 96 h of catalysis, and the strain showed favorable tolerance to glycolic acid. A positive mutant strain P. kudriavzevii GSUV-7 was obtained through UV mutagenesis and high-throughput screening, whose glycolic acid productivity was 2.90-fold higher than that of the original strain. In a 5-L fermenter, P. kudriavzevii GSUV-7 produced 117.60 g/L of glycolic acid after 106 h of catalysis, with a 100% conversion rate. [Conclusion] This study successfully obtains a mutant strain P. kudriavzevii GSUV-7 with a high yield of glycolic acid, providing strain resources and new insights for the research on biosynthesis of glycolic acid.

Eumelanin, a natural biological pigment formed by the polymerization of 5,6-dihydroxyindole and its carboxylic acid derivatives, is ubiquitous in animals and microorganisms. Its highly conjugated molecular structure confers multiple functional properties, including broad-spectrum light absorption, antioxidant activity, free radical scavenging, and metal ion chelation, making it a promising material for applications in biomedicine, functional coatings, and environmental remediation. The conventional production of eumelanin relies largely on extraction from animal tissue or chemical synthesis, which are constrained by limited raw materials and uncontrollable product structures. Recently, microbial cell factory-based biosynthesis of eumelanin has attracted increasing attention due to its environmental sustainability and structural controllability. This review comprehensively summarizes the biosynthetic pathways, strategies for metabolic engineering and genetic engineering, analysis and characterization methods for eumelanin, and discusses future perspectives for the application and development of microbial eumelanin production.

Ulcerative colitis (UC) is a chronic non-specific intestinal inflammatory disease with complex pathogenesis. Recent studies have identified a pivotal role of the gut microbiota in the etiology of the disease. Beneficial bacteria, such as Lactobacillus and Bifidobacterium, have been shown to regulate the balance of the gut microbiota, repair the mucosal barrier, and alleviate inflammation. In contrast, excessive proliferation or secretion of toxins by harmful bacteria, such as Escherichia, can damage the integrity of the mucosa, induce inflammation, and accelerate the progression of UC. The active ingredients of traditional Chinese medicine, such as Scutellariae radix polysaccharides, pulchinenosides, and ginsenoside Rg1, may offer a promising avenue for the treatment of UC by modulating the structure of the gut microbiota and enhancing the barrier function and mucosal integrity. The present article reviews the latest research progress in the regulation mechanism of the gut microbiota in UC and the traditional Chinese medicine intervention, with a view to providing new strategies and theoretical support for clinical treatment.

Medicinal plants and microorganisms engage in complex, dynamic interactions that profoundly influence plant growth and development, the biosynthesis of secondary metabolites, resistance to pathogens, and adaptation to environmental stressors. Therefore, elucidating the chemical signaling molecules that mediate these interactions is of fundamental importance. The review systematically summarizes the types and functional mechanisms of chemical signals involved in medicinal plant-microorganism interactions. It highlights the roles of both plant- and microorganism-derived signaling molecules in shaping the rhizosphere microbial community assembly, regulating plant growth, and modulating the accumulation of bioactive secondary metabolites. In addition, we discuss the functional divergence of bidirectional signaling in both symbiotic and competitive interactions. Although many mechanism aspects of these chemical signals remain to be fully elucidated, current knowledge provides a solid framework for understanding their regulatory roles. With a “signal-microbiome-function” framework, it is possible to manipulate plant chemical signaling or screen functional microbial strains to reconstruct beneficial rhizosphere microbiomes. Such strategies hold potential for improving soil-plant-microorganism interactions, promoting plant growth, enhance the accumulation of medicinal compounds, and strengthen resistance to pathogens. Overall, these insights are of considerable significance for improving the quality of Chinese medicinal materials and promoting the sustainable and ecological cultivation of medicinal plants.