MOESM1 of Identification and utilization of two important transporters: SgvT1 and SgvT2, for griseoviridin and viridogrisein biosynthesis in Streptomyces griseoviridis

Additional file 1: Figure S1. The multiple alignment of SgvT1/T3 with other transporters. Figure S2. The multiple alignment of SgvT2 with other transporters. Figures S3–S5. The inactivation of sgvT1-T3. Figure S6–S8. HPLC analyses of the fermentation extract of Wild-type & ΔsgvT1-T3. Figure S9. HPLC analyses of the fermentation extract of WT::sgvT1–T2. Figure S10. The HPLC standard curve of GV/ VG. Figure S11. HPLC analyses of fermentation extract of complemented mutants. Table S1. Primer pairs used for PCR-targeting of sgvT1–T3. Table S2. Primers used for PCR confirmation of double-crossover mutants. Table S3. Primer pairs used for complementation of sgvT1–T3. Table S4. Primer pairs used for RT-PCR. Table S5. Primer pairs used for qPCR. Table S6. Quantitative analysis of GV/VG production

Discovery of a New Family of Dieckmann Cyclases Essential to Tetramic Acid and Pyridone-Based Natural Products Biosynthesis

Bioinformatic analyses indicate that TrdC, SlgL, LipX₂, KirHI, and FacHI belong to a group of highly homologous proteins involved in biosynthesis of actinomycete-derived tirandamycin B, streptolydigin, α-lipomycin, kirromycin, and factumycin, respectively. However, assignment of their biosynthetic roles has remained elusive. Gene inactivation and complementation, <i>in vitro</i> biochemical assays with synthetic analogues, point mutations, and phylogenetic tree analyses reveal that these proteins represent a new family of Dieckmann cyclases that drive tetramic acid and pyridone scaffold biosynthesis

Identification of the Biosynthetic Gene Cluster for the Anti-infective Desotamides and Production of a New Analogue in a Heterologous Host

The desotamides (DSAs) are potent antibacterial cyclohexapeptides produced by <i>Streptomyces scopuliridis</i> SCSIO ZJ46. We have identified the 39-kb <i>dsa</i> biosynthetic gene cluster by whole-genome scanning. Composed of 17 open reading frames, the cluster codes for four nonribosomal peptide synthetases and associated resistance, transport, regulatory, and precursor biosynthesis proteins. Heterologous expression of the <i>dsa</i> gene cluster in <i>S. coelicolor</i> M1152 afforded desotamides A and B and the new desotamide G. Cluster identification and its demonstrated amenability to heterologous expression provide the foundation for future mechanistic studies as well as the generation of new and potentially clinically significant DSA analogues

MOESM1 of Characterization and heterologous expression of the neoabyssomicin/abyssomicin biosynthetic gene cluster from Streptomyces koyangensis SCSIO 5802

Additional file 1: Table S1. Bacteria used in this study. Table S2. Plasmids used in this study. Table S3. Primers used in this study. Figure S1. Chemical structures of tetronate-containing natural products and the unique set of five highly conserved genes responsible for tetronate biosynthesis. Figure S2. HPLC analyses of fermentation extracts of the inactivated mutants of boundary genes. Figure S3. Alignments of seven KS domains of AbmB1–B3. Figure S4. Alignments of five KR domains of AbmB1–B2. Figure S5. Alignments of five DH domains of AbmB1–B2. Figure S6. Alignments of five AT domains of AbmB1–B2. Figure S7. Alignments of AbmT with the typical type II TEs. Figure S8. The 14 transmembrane helices of AbmD. Figure S9. Alignments of AbmI with previously characterized SARP regulators. Figure S10. Alignments of AbmH with previously characterized LuxR-regulators. Figure S11. The quantitative HPLC standard curve for abyssomicin 2. Figures S12–S30. Disruption of 19 abm-related genes in wild-type S. koyangensis SCSIO 5802 via PCR-targeting

Data_Sheet_1_Effect of acupuncture for non-motor symptoms in patients with Parkinson’s disease: A systematic review and meta-analysis.doc

BackgroundAlthough non-motor symptoms of Parkinson’s disease (PD) are serious, effective treatments are still lacking. Acupuncture may have clinical benefits for non-motor symptoms of PD patients, but high-quality evidence supporting this possibility is still limited. Hence, we conducted this meta-analysis to evaluate the effect of acupuncture treatment on non-motor symptoms in patients with PD.MethodsRandomized controlled trials (RCTs) of acupuncture treatment for PD were retrieved from the following electronic databases: Medline (OVID), Embase (OVID), Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese BioMedical Literature Database, Chonqing VIP (CQVIP), and Wangfang database. Studies evaluating non-motor symptoms of PD were retrieved. Methodological quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions.ResultsA total of 27 RCTs were included, among which 8 outcomes related to non-motor symptoms were evaluated. The results showed that acupuncture combined with medication had benefits for PD-related insomnia relative to medication alone or sham acupuncture [standardized mean difference (SMD) = 0.517; 95% confidence interval (CI) = 0.242–0.793; p = 0.000], and acupuncture treatment had benefits at 8 weeks (SMD = 0.519; 95% CI = 0.181–0.857; p = 0.003). Regarding depression, acupuncture treatment was more effective (SMD = −0.353; 95% CI = −0.669 to −0.037; p = 0.029) within 2 months (SMD = −0.671; 95% CI = −1.332 to −0.011; p = 0.046). Regarding cognition, quality of life, and Unified Parkinson’s Disease Rating Scale (UPDRS) I and II scores, acupuncture treatment was effective [SMD = 0.878, 95% CI = 0.046–1.711, p = 0.039; SMD = −0.690, 95% CI = −1.226 to −0.155, p = 0.011; weighted mean difference (WMD) = −1.536, 95% CI = −2.201 to −0.871, p = 0.000; WMD = −2.071, 95% CI = −3.792 to −0.351, p = 0.018; respectively]. A significant difference was not found in terms of PD-related constipation. Only one study evaluated PD-related fatigue.ConclusionThe results of the analysis suggested that acupuncture treatment could ameliorate the symptoms of depression, quality of life, cognition, total mentation, behavior and mood, and activities of daily living in PD patients. Nevertheless, more prospective, well-designed RCTs with larger sample sizes are required to confirm our findings.</p

Deciphering the Biosynthetic Origin of l-<i>allo</i>-Isoleucine

The nonproteinogenic amino acid l-<i>allo</i>-isoleucine (l-<i>allo</i>-Ile) is featured in an assortment of life forms comprised of, but not limited to, bacteria, fungi, plants and mammalian systems including <i>Homo sapiens</i>. Despite its ubiquity and functional importance, the specific origins of this unique amino acid have eluded characterization. In this study, we describe the discovery and characterization of two enzyme pairs consisting of a pyridoxal 5′-phosphate (PLP)-linked aminotransferase and an unprecedented isomerase synergistically responsible for the biosynthesis of l-<i>allo</i>-Ile from l-isoleucine (l-Ile) in natural products. DsaD/DsaE from the desotamide biosynthetic pathway in <i>Streptomyces scopuliridis</i> SCSIO ZJ46, and MfnO/MfnH from the marformycin biosynthetic pathway in <i>Streptomyces drozdowiczii</i> SCSIO 10141 drive l-<i>allo</i>-Ile generation in each respective system. In vivo gene inactivations validated the importance of the DsaD/DsaE pair and MfnO/MfnH pair in l-<i>allo</i>-Ile unit biosynthesis. Inactivation of PLP-linked aminotransferases DsaD and MfnO led to significantly diminished desotamide and marformycin titers, respectively. Additionally, inactivation of the isomerase genes <i>dsaE</i> and <i>mfnH</i> completely abolished production of all l-<i>allo</i>-Ile-containing metabolites in both biosynthetic pathways. Notably, in vitro biochemical assays revealed that DsaD/DsaE and MfnO/MfnH each catalyze a bidirectional reaction between l-<i>allo</i>-Ile and l-Ile. Site-directed mutagenesis experiments revealed that the enzymatic reaction involves a PLP-linked ketimine intermediate and uses an arginine residue from the <i>C</i>-terminus of each isomerase to epimerize the amino acid β-position. Consequently, these data provide important new insight into the origins of l-<i>allo</i>-Ile in natural products with medicinal potential and illuminate new possibilities for biotool development

Enzymatic Synthesis of GDP-α‑l‑fucofuranose by MtdL and Hyg20

Two mutases, MtdL and Hyg20, are reported. Both are able to functionally drive the biosynthesis of GDP-α-l-fucofuranose. Both enzymes catalyze similar functions, catalytically enabling the bidirectional reaction between GDP-β-l-fucopyranose and GDP-α-l-fucofuranose using only divalent cations as cofactors. This realization is but one of a number of important insights into fucofuranose biosynthesis presented herein

Data_Sheet_1_Dietary vitamin E intake and risk of Parkinson's disease: a cross-sectional study.docx

ObjectiveCurrent evidence on the association between dietary vitamin E intake and the risk of Parkinson's disease (PD) is limited. The aim of the study was to explore the association of dietary vitamin E intake with PD in the United States among adults over 40 years.MethodsWe conducted a cross-sectional study with data collected from National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. A total of the sample of 13,340 participants were included. To identify the different characteristics of the participants, we utilized propensity score matching (PSM) to reduce the effects of selection bias and confounding variables. Weighted univariate and multivariable logistic regression were used to examine the association between dietary vitamin E intake and PD before and after matching. Then, restricted cubic spline (RCS) was used to visually describe the possible non-linear relationships. Finally, we employed the subgroup analysis to further investigate the relationship between dietary vitamin E intake and PD.ResultsAccording to the weighted univariate and multivariable logistic regression analysis, vitamin E intake was inversely associated with the risk of PD before and after matching. The results of RCS analysis revealed no non-linear inverse relationship between vitamin E intake and PD before and after matching. The subgroup analysis showed that age may influence the negative association between vitamin E and PD (P ConclusionAmong participants over 40 years of age, vitamin E intake was negatively associated with the risk of PD. Our data may support the supplementation of vitamin E to be used as an intervention strategy for the occurrence of PD.</p

Biosynthetic Baeyer–Villiger Chemistry Enables Access to Two Anthracene Scaffolds from a Single Gene Cluster in Deep-Sea-Derived <i>Streptomyces olivaceus</i> SCSIO T05

Four known compounds, rishirilide B (<b>1</b>), rishirilide C (<b>2</b>), lupinacidin A (<b>3</b>), and galvaquinone B (<b>4</b>), representing two anthracene scaffolds typical of aromatic polyketides, were isolated from a culture of the deep-sea-derived <i>Streptomyces olivaceus</i> SCSIO T05. From the <i>S. olivaceus</i> producer was cloned and sequenced the <i>rsd</i> biosynthetic gene cluster (BGC) that drives rishirilide biosynthesis. The structural gene <i>rsdK</i>₂ inactivation and heterologous expression of the <i>rsd</i> BGC confirmed the single <i>rsd</i> BGC encodes construction of <b>1</b>–<b>4</b> and, thus, accounts for two anthracene scaffolds. Precursor incubation experiments with ¹³C-labeled acetate revealed that a Baeyer–Villiger-type rearrangement plays a central role in construction of <b>1</b>–<b>4</b>. Two luciferase monooxygenase components, along with a reductase component, are presumably involved in the Baeyer–Villiger-type rearrangement reaction enabling access to the two anthracene scaffold variants. Engineering of the <i>rsd</i> BGC unveiled three SARP family transcriptional regulators, enhancing anthracene production. Inactivation of <i>rsdR</i>₄, a MarR family transcriptional regulator, failed to impact production of <b>1</b>–<b>4</b>, although production of <b>3</b> was slightly improved; most importantly <i>rsdR</i>₄ inactivation led to the new adduct <b>6</b> in high titer. Notably, inactivation of <i>rsdH</i>, a putative amidohydrolase, substantially improved the overall titers of <b>1</b>–<b>4</b> by more than 4-fold

AbmV Catalyzes Tandem Ether Installation and Hydroxylation during Neoabyssomicin/Abyssomicin Biosynthesis

Members of the abyssomicin class of natural products are characterized by a novel vinylic bridged ether ring. In this study, in vivo gene inactivation, structure elucidation of the accumulated intermediate abyssomicin 6, and in vitro enzyme assays enabled the identification of a cytochrome P450 enzyme, AbmV. AbmV carries out domino reactions involving bridged ether installation and C-11 hydroxylation during the biosynthesis of neoabyssomicins/abyssomicins in <i>S. koyangensis</i> SCSIO 5802