[Advances in synthesis of succinic acid using yeast cell factories].

Succinic acid is an important C4 platform compound that serves as a raw material for the production of 1,4-butanediol, tetrahydrofuran, and biodegradable plastics such as polybutylene succinate (PBS). Compared to the traditional petrochemical-based route that uses maleic anhydride as a raw material, the microbial fermentation method for producing succinic acid offers more sustainable economic value and environmental friendliness. Yeasts with good acid tolerance can achieve low-pH fermentation of succinic acid, significantly reducing the cost of product extraction. Therefore, constructing high-yield succinic acid yeast strains through metabolic engineering has garnered increasing attention. This paper systematically introduced the application value and market size of succinic acid, summarized the pathways and key enzymes involved in succinic acid synthesis in microorganisms, and elaborated on the latest research progress in the synthesis of succinic acid using yeast cell factories. It also presented the current status of succinic acid synthesis using non-food raw materials such as glycerol, acetic acid, lignocellulosic hydrolysate, and others as substrates by engineered yeast strains. Finally, the paper provided a prospect for low-pH succinic acid biomanufacturing based on yeast cell factories.

Perturbations in gut microbiota composition in schizophrenia.

Schizophrenia is a severe, complex and long-term psychiatric disorder with unclear etiology. Gut microbes influence the central nervous system via the gut-brain axis. Consequently, investigations of the relationship between gut microbes and schizophrenia are warranted. This study involved 29 patients with schizophrenia and 30 age-matched normal controls. After 16S rRNA gene sequencing and whole-genome shotgun metagenomic sequencing, we analyzed microbial diversity, composition, and function. According to 16S rRNA and metagenomic gene sequencing results, patients with schizophrenia had higher abundances of Clostridium and Megasphaera. Functional analysis showed that sphingolipid, phosphonates and phosphinates, as well as glutamine metabolism were associated with the occurrence and development of schizophrenia. Our data suggest that the gut microbiota exerts an effect on patients with schizophrenia, providing valuable insights into the potential regulation of in the context of this disorder.

Sustainable succinic acid production from lignocellulosic hydrolysates by engineered strains of Yarrowia lipolytica at low pH.

Succinic acid (SA) is a valuable C4 platform chemical with diverse applications. Lignocellulosic biomass represents an abundant and renewable carbon resource for microbial production of SA. However, the presence of toxic compounds in pretreated lignocellulosic hydrolysates poses challenges to cell metabolism, leading to inefficient SA production. Here, engineered Yarrowia lipolytica Hi-SA2 was shown to utilize glucose and xylose from corncob hydrolysate to produce 32.6 g/L SA in shaking flasks. The high concentration of undetoxified hydrolysates significantly inhibited yeast growth and SA biosynthesis, with furfural identified as the key inhibitor. Through overexpressing glutathione synthetase encoding gene YlGsh2, the tolerance of engineered strain to furfural and toxic hydrolysate was significantly improved. In a 5-L bioreactor, Hi-SA2-YlGsh2 strain produced 45.34 g/L SA within 32 h, with a final pH of 3.28. This study provides a sustainable process for bio-based SA production, highlighting the efficient SA synthesis from lignocellulosic biomass through low pH fermentation.

Reconfiguration of the reductive TCA cycle enables high-level succinic acid production by Yarrowia lipolytica.

Succinic acid (SA) is an important C4-dicarboxylic acid. Microbial production of SA at low pH results in low purification costs and hence good overall process economics. However, redox imbalances limited SA biosynthesis from glucose via the reductive tricarboxylic acid (TCA) cycle in yeast. Here, we engineer the strictly aerobic yeast Yarrowia lipolytica for efficient SA production without pH control. Introduction of the reductive TCA cycle into the cytosol of a succinate dehydrogenase-disrupted yeast strain causes arrested cell growth. Although adaptive laboratory evolution restores cell growth, limited NADH supply restricts SA production. Reconfiguration of the reductive SA biosynthesis pathway in the mitochondria through coupling the oxidative and reductive TCA cycle for NADH regeneration results in improved SA production. In pilot-scale fermentation, the engineered strain produces 111.9 g/L SA with a yield of 0.79 g/g glucose within 62 h. This study paves the way for industrial production of biobased SA.

Analysis of the effect of anti-tuberculosis therapy combined with all-in-one nursing care on the alleviation of inflammation in patients with pulmonary tuberculosis.

To analyze the application effect of anti-tuberculosis therapy (ATT) combined with all-in-one nursing care on pulmonary tuberculosis (PT). Seventy-four PT patients who received ATT in our hospital between December 2015 and June 2016 were selected as the research participants and randomized into a research group (RG; n=37) and a control group (CG; n=37) that were given all-in-one nursing care and routine care, respectively. The cure rate and treatment compliance were compared between groups, and the awareness of disease prevention and treatment was investigated. Patients' psychological status and quality of life were evaluated using the Self-Rating Depression/Anxiety Scale (SAS/SDS) and the Quality of Life Questionnaire Core 30 (QLQ-C30), respectively. RG and CG were not statistically different in the clinical cure rate (P>0.05), but the X-ray cure rate was higher and the recurrence rate was lower in RG (P<0.05). In addition, RG showed higher medication compliance rate, regular reexamination rate and awareness of disease prevention and treatment than CG (P<0.05). Reductions in SAS/SDS scores were observed in both groups after care, with even lower levels in RG, while the QLQ-C30 score increased and was higher in RG as compared to CG (P<0.05). Therefore, All-in-one nursing care can effectively enhance the level of treatment compliance and awareness of disease prevention and treatment of PT patients. In the future, when treating PT patients in the clinic, the effectiveness of ATT can be improved by implementing all-in-one nursing care to provide more reliable prognosis for patients.

Biosynthesis of α-Pinene by Genetically Engineered Yarrowia lipolytica from Low-Cost Renewable Feedstocks.

α-Pinene, an important biologically active natural monoterpene, has been widely used in fragrances, medicines, and fine chemicals, especially, in high-density renewable fuels such as jet fuel. The development of an α-pinene production platform in a highly modifiable microbe from renewable substitute feedstocks could lead to a green, economical avenue, and sustainable biotechnological process for the biosynthesis of α-pinene. Here, we report engineering of an orthogonal biosynthetic pathway for efficient production of α-pinene in oleaginous yeast Yarrowia lipolytica that resulted in an α-pinene titer of 19.6 mg/L when using glucose as the sole carbon source, a significant 218-fold improvement than the initial titer. In addition, the potential of using waste cooking oil and lignocellulosic hydrolysate as carbon sources for α-pinene production from the engineered Y. lipolytica strains was analyzed. The results indicated that α-pinene titers of 33.8 and 36.1 mg/L were successfully obtained in waste cooking oil and lignocellulosic hydrolysate medium, thereby representing the highest titer reported to date in yeast. To our knowledge, this is also the first report related to microbial production of α-pinene from waste cooking oil and lignocellulosic hydrolysate.