Genome-Based Mining of Carpatamides I-M and Their Candidate Biosynthetic Gene Cluster.

Chemically investigating the marine-derived 1268 led to the isolation of a new compound of carpatamide I (). Subsequent genomic analysis identified its candidate biosynthetic gene cluster of approximately 44 kb. In order to obtain more carpatamide derivatives, we conducted the upregulation of Ctd14, which is a positive regulator, and obtained improvement of carpatamide I and four new compounds of carpatamides J-M (-).

Discovery of olimycin E from sp. 11695.

A new natural product olimycin E (), together with two known compounds of divergolide R () and olimycin B (), were obtained from the marine-derived 11695. The structures of were established on the basis of HRESIMS as well as 1D and 2D NMR datasets. The absolute configuration of is identified as 4 R, 6S, 7S, 10 R by comparison the experiment ECD with that of the theoretical ECD.

Methylation in hangtaimycin biosynthesis and its antibacterial activities.

About two-thirds of small molecule drugs contain methyl group and it plays a very important role in the drug development. So, methyltransferases catalyzing the methylation have always attracted great attention. Hangtaimycin (HTM) is a potent hepatoprotective agent.

BamA-targeted antimicrobial peptide design for enhanced efficacy and reduced toxicity.

The emergence of drug-resistant superbugs has necessitated a pressing need for innovative antibiotics. Antimicrobial peptides (AMPs) have demonstrated broad-spectrum antibacterial activity, reduced susceptibility to resistance, and immunomodulatory effects, rendering them promising for combating drug-resistant microorganisms. This study employed computational simulation methods to screen and design AMPs specifically targeting ESKAPE pathogens.

Virtual screening and biological activity evaluation of novel efflux pump inhibitors targeting AdeB.

The AdeABC efflux pump is an important mechanism causing multidrug resistance in Acinetobacter baumannii, and its main component AdeB can recognize carbapenems, aminoglycosides, and other multi-class antibiotics and efflux them intracellularly, which is an ideal target for the development of anti-multidrug resistant bacteria drugs. Here, we combined multiple computer-aided drug design methods to target AdeB to identify promising novel structural inhibitors. Virtual screening was performed by molecular docking and molecular dynamics simulation (MD) and 12 potential compounds were identified from the databases.

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites.

An improved synthesis for tryptophan-dehydrobutyrine diketopiperazine (TDD), a co-metabolite of the hybrid polyketide/non-ribosomal peptide hangtaimycin, starting from ʟ-tryptophan is presented. Comparison to TDD isolated from the hangtaimycin producer confirmed its configuration. The X-ray structure of the racemate shows an interesting dimerisation through hydrogen bridges.

Subtly manipulating Zn-coordinated configurations with a complexing agent to boost the reversibility of the zinc anode.

By using ethylenediamine (En) as a complexing agent, the impact of various Zn coordinated configurations on Zn anode reversibility was systematically studied. With the predominant configurations of [Zn(En)] and [Zn(En)] in the electrolyte, both symmetric Zn/Zn cells and Zn/NiHCF full cells exhibit significantly improved cycling stability compared to the counterparts with pure ZnSO electrolyte.

The Mechanism of Dehydrating Bimodules in trans-Acyltransferase Polyketide Biosynthesis: A Showcase Study on Hepatoprotective Hangtaimycin.

A bioassay-guided fractionation led to the isolation of hangtaimycin (HTM) from Streptomyces spectabilis CCTCC M2017417 and the discovery of its hepatoprotective properties. Structure elucidation by NMR suggested the need for a structural revision. A putative HTM degradation product was also isolated and its structure was confirmed by total synthesis.

Two new streptovaricin derivatives from mutants of CCTCC M2017417.

Two new ansamycin derivatives, damavaricin H () and protostreptovaricin VI () were isolated from the CCTCC M2017417 derived mutants of ΔstvP5 and ΔstvA2, respectively. The structures of and were established by analysis of the HRESIMS as well as 1D and 2D NMR datasets. The minimum inhibitory concentration (MIC) results showed that compounds and possessed the corresponding anti-MRSA bioactivities of 4 ∼ 8 μg/ml and 8 ∼ 16 μg/ml, which confirmed the structure-activity relationships of streptovaricins reported previously and also revealed that addition of the hydroxyl group at C-8 increased the anti-MRSA activity.

Uncovering the cytochrome P450-catalyzed methylenedioxy bridge formation in streptovaricins biosynthesis.

Streptovaricin C is a naphthalenic ansamycin antibiotic structurally similar to rifamycins with potential anti-MRSA bioactivities. However, the formation mechanism of the most fascinating and bioactivity-related methylenedioxy bridge (MDB) moiety in streptovaricins is unclear. Based on genetic and biochemical evidences, we herein clarify that the P450 enzyme StvP2 catalyzes the MDB formation in streptovaricins, with an atypical substrate inhibition kinetics.

Antibacterial natural products lobophorin L and M from the marine-derived sp. 4506.

Two new spirotetronate natural products, lobophorin L () and lobophorin M (), together with three known lobophorin-like spirotetronate antibiotics (-) and two known ansamycins (-), were isolated from the marine-derived sp. 4506. The structures of and were established on the basis of HRESIMS as well as 1D and 2D NMR datasets.

Natural Hydroxamate-Containing Siderophore Acremonpeptides A-D and an Aluminum Complex of Acremonpeptide D from the Marine-Derived SCSIO 115.

Four new hydroxamate-containing natural product cyclopeptides designated acremonpeptides A-D (-), together with Al(III)-acremonpeptide D () were obtained from the marine fungus SCSIO 115. The planar structures of - were established on the basis of HRMS as well as 1D and 2D NMR data sets. Moreover, the amino acid absolute configurations were determined using Marfey's method.

A mycophenolic acid derivative from the fungus sp. SCSIO sof101.

Mycophenolic acid (MPA) is a group of metabolite derived from several species of , which shows potent bioactivity. In this study, a new derivative of MPA compound named penicacid D (), was isolated from the marine derived fungus sp. SCSIO sof101, along with seven known compounds ().

Specific cancer stem cell-therapy by albumin nanoparticles functionalized with CD44-mediated targeting.

Background: Cancer stem cells (CSCs) are highly proliferative and tumorigenic, which contributes to chemotherapy resistance and tumor occurrence. CSCs specific therapy may achieve excellent therapeutic effects, especially to the drug-resistant tumors.

Results: In this study, we developed a kind of targeting nanoparticle system based on cationic albumin functionalized with hyaluronic acid (HA) to target the CD44 overexpressed CSCs.

Sol-Gel Synthesis and in Situ X-ray Diffraction Study of LiNdWO as a Lithium Container.

In this work, garnet-framework LiNdWO as a novel insertion-type anode material has been prepared via a facile sol-gel method and examined as a lithium container for lithium ion batteries (LIBs). LiNdWO shows a charge capacity of 225 mA h g at 50 mA g, and with the current density increasing up to 500 mA g, the charge capacity can still be maintained at 186 mA h g. After cycling at 500 mA g for 500 cycles, LiNdWO retains about 85% of its first charge capacity changed from 190.

Cytochalasan and Tyrosine-Derived Alkaloids from the Marine Sediment-Derived Fungus Westerdykella dispersa and Their Bioactivities.

Six new cytochalasans, designated as 18-oxo-19,20-dihydrophomacin C (1), 18-oxo-19-methoxy-19,20- dihydrophomacin C (2), 18-oxo-19-hydroxyl-19,20-dihydrophomacin C (3), 19,20-dihydrophomacin C (4), 19-methoxy-19,20-dihydrophomacin C (5), 19-hydroxyl-19,20-dihydrophomacin C (6), and one new tyrosine-derived alkaloid named as gymnastatin Z (8), together with two known compounds, phomacin B (7) and triticone D (9), were isolated from a solid-substrate fermentation culture of Westerdykella dispersa which was derived from marine sediments. Their structures were established on the basis of spectroscopic analysis using 1D and 2D NMR techniques, and comparison of NMR data to those of known compounds. The anti-bacterial and cytotoxic activities assays of all isolated compounds were evaluated against eight human pathogenic bacteria and five human cancer cell lines, respectively.

Amino Acid Conjugated Anthraquinones from the Marine-Derived Fungus Penicillium sp. SCSIO sof101.

Emodacidamides A-H (1-8), natural products featuring anthraquinone-amino acid conjugates, have been isolated from a marine-derived fungus, Penicillium sp. SCSIO sof101, together with known anthraquinones 9 and 10. The planar structures of 1-8 were elucidated using a combination of NMR spectroscopy and mass spectrometry.

Circulating Tumor Cells: From Theory to Nanotechnology-Based Detection.

Cancer stem cells with stem-cell properties are regarded as tumor initiating cells. Sharing stem-cell properties, circulating tumor cells (CTCs) are responsible for the development of metastasis, which significant affects CTC analysis in clinical practice. Due to their extremely low occurrence in blood, however, it is challenging to enumerate and analyze CTCs.

Synergistic active targeting of dually integrin αvβ3/CD44-targeted nanoparticles to B16F10 tumors located at different sites of mouse bodies.

Conventional enhanced permeation and retention (EPR) mediates the effects of many drugs, including the accumulation of nanocarriers at tumor sites, but its efficiency remains low. In this study, this limitation was overcome by developing a dual-targeting delivery system based on hyaluronan (HA, a major ligand of CD44) and tetraiodothyroacetic acid (tetrac, a specific ligand of αvβ3), which was exploited to carry docetaxel (DTX) for the synergistic active targeting to tumors. First, a tetrac-HA (TeHA) conjugate was synthesized and grafted onto the surfaces of solid lipid nanoparticles (SLNs) (TeHA-SLNs/DTX), with a high encapsulation efficiency of >91.

A new diketopiperazine derivative from a deep sea-derived Streptomyces sp. SCSIO 04496.

A new diketopiperazine (DKP) derivative, (6R,3Z)-3-benzylidene-6-isobutyl-1-methyl piperazine-2,5-dione (1), as well as five known DKPs 2-6 was isolated from a deep sea-derived Streptomyces sp. SCSIO 04496. The structure of 1 was elucidated using a combination of 1D and 2D NMR, HR-ESI-MS and chiral-phase HPLC techniques.

Identification of the grincamycin gene cluster unveils divergent roles for GcnQ in different hosts, tailoring the L-rhodinose moiety.

The gene cluster responsible for grincamycin (GCN, 1) biosynthesis in Streptomyces lusitanus SCSIO LR32 was identified; heterologous expression of the GCN cluster in S. coelicolor M512 yielded P-1894B (1b) as a predominant product. The ΔgcnQ mutant accumulates intermediate 1a and two shunt products 2a and 3a bearing L-rhodinose for L-cinerulose A substitutions.

Biosynthesis of 9-methylstreptimidone involves a new decarboxylative step for polyketide terminal diene formation.

9-Methylstreptimidone is a glutarimide antibiotic showing antiviral, antifungal, and antitumor activities. Genome scanning, bioinformatics analysis, and gene inactivation experiments reveal a gene cluster responsible for the biosynthesis of 9-methylstreptimidone in Streptomyces himastatinicus. The unveiled machinery features both acyltransferase- and thioesterase-less iterative use of module 5 as well as a branching module for glutarimide generation.

Effects of arctiin on streptozotocin-induced diabetic retinopathy in Sprague-Dawley rats.

Diabetic retinopathy is one of the most common and severe complications of diabetes mellitus. Arctiin, a bioactive compound isolated from the dry seeds of Arctium lappa L., has been reported to have antidiabetic activity.

Halogenated anthraquinones from the marine-derived fungus Aspergillus sp. SCSIO F063.

Metabolomic investigations focusing on the marine-derived fungus Aspergillus sp. SCSIO F063 have unveiled seven new chlorinated anthraquinones (1-7) related to averantin, together with five known analogues (11-15) when the fungus was fermented using sea salt-containing potato dextrose broth. Through the addition of sodium bromide to the broth, two new brominated anthraquinones (8, 9) and one new nonhalogenated anthraquinone (10) were obtained from the fungal mycelia.

Discovery and engineered overproduction of antimicrobial nucleoside antibiotic A201A from the deep-sea marine actinomycete Marinactinospora thermotolerans SCSIO 00652.

Marinactinospora thermotolerans SCSIO 00652, originating from a deep-sea marine sediment of the South China Sea, was discovered to produce antimicrobial nucleoside antibiotic A201A. Whole-genome scanning and annotation strategies enabled us to localize the genes responsible for A201A biosynthesis and to experimentally identify the gene cluster; inactivation of mtdF, an oxidoreductase gene within the suspected gene cluster, abolished A201A production. Bioinformatics analysis revealed that a gene designated mtdA furthest upstream within the A201A biosynthetic gene cluster encodes a GntR family transcriptional regulator.