Metabolic engineering of yeasts for green and sustainable production of bioactive ginsenosides F2 and 3β,20S-Di-O-Glc-DM

Both natural ginsenoside F2 and unnatural ginsenoside 3β,20S-Di-O-Glc-DM were reported to exhibit anti-tumor activity. Traditional approaches for producing them rely on direct extraction from Panax ginseng, enzymatic catalysis or chemical synthesis, all of which result in low yield and high cost. Metabolic engineering of microbes has been recognized as a green and sustainable biotechnology to produce natural and unnatural products. Hence we engineered the complete biosynthetic pathways of F2 and 3β,20S-Di-O-Glc-DM in Saccharomyces cerevisiae via the CRISPR/Cas9 system. The titers of F2 and 3β,20S-Di-O-Glc-DM were increased from 1.2 to 21.0 mg/L and from 82.0 to 346.1 mg/L at shake flask level, respectively, by multistep metabolic engineering strategies. Additionally, pharmacological evaluation showed that both F2 and 3β,20S-Di-O-Glc-DM exhibited anti-pancreatic cancer activity and the activity of 3β,20S-Di-O-Glc-DM was even better. Furthermore, the titer of 3β,20S-Di-O-Glc-DM reached 2.6 g/L by fed-batch fermentation in a 3 L bioreactor. To our knowledge, this is the first report on demonstrating the anti-pancreatic cancer activity of F2 and 3β,20S-Di-O-Glc-DM, and achieving their de novo biosynthesis by the engineered yeasts. Our work presents an alternative approach to produce F2 and 3β,20S-Di-O-Glc-DM from renewable biomass, which lays a foundation for drug research and development.

The glycosyltransferases involved in triterpenoid saponin biosynthesis: a review / 生物工程学报

Triterpenoid saponins are widely used in medicine, health cares, cosmetics, food additives and agriculture because of their unique chemical properties and rich pharmacological activities. UDP-dependent glycosyltransferases (UGTs) are the key enzymes involved in triterpenoid saponin biosynthesis, and play important roles in the diversity of triterpenoid saponin structures and pharmacological activities. This review summarized the UGTs involved in plant triterpenoid saponin biosynthesis based on the sources of UGTs and the types of receptors. Moreover, the application of UGTs in heterologous biosynthesis of triterpenoid saponins based on synthetic biology was also discussed.

Advances in biosynthesis of cadinane sesquiterpenes / 生物工程学报

Cadinanes are a class of bicyclic sesquiterpenes with complex stereochemistry and broad pharmacological activities, such as antibacterial, anti-inflammatory, and hypoglycemic activities. To date, structurally diverse and bioactive cadinane sesquiterpenes have been isolated and identified from a variety of plants and microorganisms. Moreover, deeper understandings on cadinane sesquiterpene synthases have been made. This article categorized the 124 new cadinanes which were published in the literatures in the past four years (2017-2020) into five structural types, and presented their pharmacological activities. We also illustrated the elucidation of the biosynthetic pathways for typical cadinanes, summarized the research progress on cadinane sesquiterpene synthases. Finally, current challenges and future prospects were proposed and discussed.

Synthetic biology of plants-derived medicinal natural products / 生物工程学报

Medicinal natural products derived from plants are usually of low content and difficult to extract and isolate. Moreover, these compounds are structurally complex, making it difficult to obtain them by environmental unfriendly chemical synthesis. Biosynthesis of medicinal natural products through synthetic biology is a novel, environment-friendly and sustainable approach. Taking terpenoids (ginsenosides, paclitaxel, artemisinin, tanshinones), alkaloids (vincristine and morphine), and flavonoids (breviscapine) as examples, this review summarizes the advances of the biosynthetic pathways and synthetic biology strategies of plant-derived medicinal natural products. Moreover, we introduce the key technologies and methods of synthetic biology used in the research of medicinal natural products, and provide future prospects in this area.

A twin study of genetic and environmental influences on relationship between attention deficit and anxiety/depression in children and adolescents / 中华流行病学杂志

Objective To understand the genetic and environmental influences on the relationship between attention deficit and anxiety/depression in children and adolescents.Methods A total of 1 062 same-sex twins aged 6-18 years were included in this study.A parent-rated child behavior checklist (CBCL) was used in the assessment.Software Mx was used to fit the univariate model of structural equation.The relationship between attention deficit and anxiety/depression was analyzed through bivariate genetic modeling.Results The genetic factor had influence on the relationship between attention deficit and anxiety/depression (rg=0.48).Shared and non-shared environmental correlation scores of attention deficit and anxiety/depression were 0.86 and 0.14 respectively.Conclusion Common genetic and shared environmental influences can explain the relationship between attention deficit and anxiety/depression in children and adolescents.

A twin study of genetic and environmental influences on relationship between attention deficit and anxiety/depression in children and adolescents / 中华流行病学杂志

Objective To understand the genetic and environmental influences on the relationship between attention deficit and anxiety/depression in children and adolescents.Methods A total of 1 062 same-sex twins aged 6-18 years were included in this study.A parent-rated child behavior checklist (CBCL) was used in the assessment.Software Mx was used to fit the univariate model of structural equation.The relationship between attention deficit and anxiety/depression was analyzed through bivariate genetic modeling.Results The genetic factor had influence on the relationship between attention deficit and anxiety/depression (rg=0.48).Shared and non-shared environmental correlation scores of attention deficit and anxiety/depression were 0.86 and 0.14 respectively.Conclusion Common genetic and shared environmental influences can explain the relationship between attention deficit and anxiety/depression in children and adolescents.

Effect of obesity intervention with socio-ecological model on anthropometric measure-ments of children and adolescents / 北京大学学报(医学版)

Objective:To study whether the socio-ecological model based on “student-school-family”three-level strategy is effective in obesity prevention. Methods: A total of 3 175 students aged 7 to 18 from 16 schools (4 urban primary schools, 4 rural primary schools, 4 urban secondary schools and 4 rural secondary schools, of which 2 intervention schools were selected, respectively ) were recruited by strati-fied cluster sampling method. A three-month intervention using “student-school-family” socio-ecological model was conducted through health education and environment improvement. The intervention contents included knowledge on obesity, healthy diet and physical activities. Their anthropometric indexes were recorded. Results:The intervention prevented obesity(OR =1. 12, P <0. 05), and was effective in waist circumference (WC) and waist-hip ratio (WHR) (adjusted difference=0. 63, 0. 02, P<0. 05). WC and WHR were reduced in girls ( adjusted difference=0 . 52 &0 . 02 , P<0 . 05 ) , and obesity was prevented in girls ( OR=1 . 18 , P<0 . 05 ) . WC and WHR were reduced in boys ( adjusted difference=0 . 73 , 0 . 01 , P<0 . 05 ) . WHR were reduced in urban areas ( adjusted difference=0 . 01 , P<0 . 05 ) . WC and WHR were reduced ( adjusted difference=1 . 05 , 0 . 02 , P<0 . 05 ) and obesity was prevented (OR=1. 18, P<0. 05) in rural areas. WHR were reduced (adjusted difference=0. 01, P<0. 05) and obesity was prevented (OR =1. 21, P <0. 05) in primary schools. WHR were reduced in secondary schools (adjusted difference=0. 02, P<0. 05). The intervention effect was better in girls than in boys, in rural areas than in urban areas, and in primary schools than in secondary schools. The overweight and obesity prevalence went down after the intervention (χ2 =11 . 01 , P <0 . 01 ) . Conclusion:Intervention strategy is effective in central obesity indexes such as WC and WHR, and it can be used widely.

Genetic analysis of gonadotropin-gonadal axis in boys: a twin study / 中华男科学杂志

<p><b>OBJECTIVE</b>To analyse the heritabilities of serum luteinizing hormone(LH), follicle-stimulating hormone (FSH), testosterone (T) and estradiol (E2) in twin boys, and to study the genetic contributions to gonadotropin-gonadal axis.</p><p><b>METHODS</b>A total of 51 pairs of male twins, 35 monozygotic (MZ) and 16 dizygotic(DZ) aged 5 to 11 years, were investigated. Serum gonadotropin and sex hormone were measured by radioimmunoassay. The twin zygosity was verified by determination of short tandem repeat amplified fragment length polymorphism systems. The genetic analysis was performed using intraclass correlation coefficient method.</p><p><b>RESULTS</b>The intraclass correlation coefficient was greater in the MZ twins than in the DZ twins. The estimated heritabilities were respectively LH 0.51, FSH 0.32, T 0.81, E2 0.41.</p><p><b>CONCLUSION</b>Genetic factors are major determinants of gonadotropin-gonadal axis in boys.</p>