ABSTRACT
Non-conventional yeasts such as Yarrowia lipolytica, Pichia pastoris, Kluyveromyces marxianus, Rhodosporidium toruloides and Hansenula polymorpha have proven to be efficient cell factories in producing a variety of natural products due to their wide substrate utilization spectrum, strong tolerance to environmental stresses and other merits. With the development of synthetic biology and gene editing technology, metabolic engineering tools and strategies for non-conventional yeasts are expanding. This review introduces the physiological characteristics, tool development and current application of several representative non-conventional yeasts, and summarizes the metabolic engineering strategies commonly used in the improvement of natural products biosynthesis. We also discuss the strengths and weaknesses of non-conventional yeasts as natural products cell factories at current stage, and prospects future research and development trends.
Subject(s)
Yeasts/genetics , Yarrowia/metabolism , Gene Editing , Metabolic EngineeringABSTRACT
Objective:To evaluate the monitoring value of amplitude-integrated electroencephalography (aEEG) in brain injury among neonates with severe hyperbilirubinemia.Methods:This study retrospectively recruited 223 full-term infants with severe hyperbilirubinemia who underwent aEEG in the Department of Neonatology of Guangzhou Women and Children Medical Center from October 2018 to June 2020. Differences in serum bilirubin level and the incidence of acute bilirubin encephalopathy (ABE) between the normal group ( n=180) and abnormal aEEG group ( n=43) were compared. The monitoring value of aEEG in ABE, and its association with brain stem auditory evoked potential (BAEP) and MRI were studied. Two-independent sample t-test, Mann-Whitney U test and Chi-square test were used for comparing the differences between groups. Goodman-Kruskal Gamma was used for correlation analysis. Results:The total serum bilirubin level [(536.2±154.6) vs (422.1±103.0) μmol/L, t=-5.109, P<0.001] and the incidence of ABE [62.8% (27/43) vs 9.4% (17/180), χ2=62.366, P<0.001] in the abnormal aEEG group were significantly higher than those in the normal aEEG group. The sensitivity and specificity of aEEG in the diagnosis of ABE were 61.3% and 91.1%, respectively. With the progression of ABE from warning period to spasmodic stage, more severe voltage suppression (Gamma=0.847, P=0.003), more disordered sleep-wake cycles (Gamma=0.941, P<0.001) and a more frequent epileptic discharge (Gamma=0.976, P<0.001) were observed. Out of the 223 cases, 148 underwent BAEP. The abnormal rate of aEEG in abnormal BAEP group was significantly higher than that in normal BAEP group [32.7% (33/101) vs 6.4% (3/47), χ2=12.040, P=0.001]. The incidence of abnormal voltage in severe abnormal BAEP group was significantly higher than that in mild abnormal BAEP group [20.6% (7/34) vs 2.6% (1/38), χ2=5.858, P=0.016]. The incidence of epileptic discharge in severe abnormal BAEP group was significantly higher than that in mild abnormal BAEP group [32.4% (11/34) vs 2.6% (1/38), χ2=11.413, P=0.001] and moderate abnormal BAEP group [32.4% (11/34) vs 3.5% (1/29), χ2=8.480, P=0.004]. Among the 223 cases, 108 received MRI examination. The incidence of epileptic discharge in the cases with bilirubin brain injury image was significantly higher than those with normal MRI images [28.6% (10/35) vs 2.6% (1/39), χ2=9.864, P=0.002] and those with other abnormal images [28.6% (10/35) vs 2.9% (1/34), χ2=8.451, P=0.004]. Conclusions:aEEG monitoring is helpful in the diagnosis of ABE and can reflect disease severity. Severe hyperbilirubinemia-induced brain injury in neonates mainly manifests as increased and more frequent epileptic discharge on aEEG. There is a correlation between aEEG monitoring with BAEP and MRI findings.