1. Chen Jianwei, Zhang Hongfang, Wang Siqi, Du Yujie, Wei Bin, Wu Qiang*, Wang Hong*. Inhibitors of bacterial extracellular vescicles. Frontiers in Microbiology. 2022. 13: 835058. （https://doi.org/10.3389/fmicb.2022.835058）IF: 5.640

Abstract

Both Gram-positive and Gram-negative bacteria can secrete extracellular vesicles (EVs), which contain numerous active substances. EVs mediate bacterial interactions with their hosts or other microbes. Bacterial EVs play a double-edged role in infections through various mechanisms, including the delivery of virulence factors, modulating immune responses, mediating antibiotic resistance, and inhibiting competitive microbes. The spread of antibiotic resistance continues to represent a difficult clinical challenge. Therefore, the investigation of novel therapeutics is a valuable research endeavor for targeting antibiotic-resistant bacterial infections. As a pathogenic substance of bacteria, bacterial EVs have gained increased attention. Thus, EV inhibitors are expected to function as novel antimicrobial agents. The inhibition of EV production, EV activity, and EV-stimulated inflammation are considered potential pathways. This review primarily introduces compounds that effectively inhibit bacterial EVs and evaluates the prospects of their application.

2. Chen Jianwei, Chen Jun, Wang Siqi, Bao Xiaoze, Li Songwei, Wei Bin,  Zhang Huawei, Wang Hong*. Amycolachromones A-F, isolated from a Streptomycin-resistant strain of the deep-sea marine Actinomycete Amycolatopsis sp. WP1. Marine Drugs. 2022. 20: 162. (https://doi.org/10.3390/md20030162) IF: 5.118

Abstract

In this study, a detailed chemical investigation of a streptomycin-resistant strain of the deep-sea marine, actinomycete Amycolatopsis sp. WP1, yielded six novel amycolachromones A–F (1–6), together with five known analogues (7–11). Amycolachromones A–B (1–2) possessed unique dimer skeletons. The structures and relative configurations of compounds 1–11 were elucidated by extensive spectroscopic data analyses combined with X-ray crystal diffraction analysis. Plausible biogenetic pathways of amycolachromones A–F were also proposed.

3. Bao Xiaoze, Wang Xingyue, Tian Jinmiao, Ye Xinyi, Wang Baomin*, Wang Hong*. Recent advances in the applications of pyrazolone derivatives in enantioselective synthesis. Organic & Biomolecular Chemistry. 2022,20, 2370-2386. (https://doi.org/10.1039/D1OB02426D) IF: 3.876

Abstract

Pyrazolones and pyrazoles, featuring nitrogen–nitrogen bonds, are two of the most important classes of heterocycles, owing to their widespread occurrence in medicinal chemistry and functional materials. The last decade has witnessed a rapid increase in the construction of chiral pyrazolone and pyrazole derivatives, with the application of pyrazolone derivatives as powerful synthons. Since our last review in 2018, a large number of new achievements has emerged in this area, requiring a timely update. Thus, this review summarizes these elegant achievements based on the multiple reactive sites of different pyrazolone synthons. In addition, important mechanisms and interesting biological investigations relating to the corresponding products are also discussed.

4. Chen Jianwei, Li Yasheng, Wang Siqi, Zhang Hongfang, Du Yujie, Wu Qiang*, Wang Hong*. Targeting Clostridioides difficile: New uses for old drugs. Drug Discovery Today. 2022, 27(2): 1862-1873. （https://doi.org/10.1016/j.drudis.2022.03.021）IF: 7.851

Abstract

Clostridioides difficile bacteria can cause life-threatening diarrhea and colitis owing to limited treatment options and unacceptably high recurrence rates among infected patients. This necessitates the development of alternative routes for C. difficile treatment. Drug repurposing with new indications represents a proven shortcut. Here, we present a refined focus on 16 FDA-approved drugs that would be suitable for further development as potential anti-C. difficile drugs. Of these drugs, clinical trials have been conducted on five currently used drugs; however, ursodeoxycholic acid is the only drug to enter Phase IV clinical trials to date. Thus, drug repurposing promotes the study of mechanistic and therapeutic strategies, providing new options for the development of next-generation anti-C. difficile agents.

5. Wei Bin#, Zhang Bo#, Du Aoqi, Zhou Zhenyi, Lu Dongze, Zhu Zhonghui, Ke Songze, Wang Sijia, Yu Yanlei, Chen Jianwei, Zhang Huawei, Jin Weihua*, Wang Hong*. Saccharina japonica fucan suppresses high fat diet-induced obesity and enriches fucoidan-degrading gut bacteria. Carbohydrate Polymers. 2022, 290: 119411. (https://www.sciencedirect.com/science/article/abs/pii/S0144861722003150) IF: 10.723

Abstract

Low molecular weight seaweed polysaccharides exhibit promising potential as novel therapeutics for the prevention of obesity and gut microbiota dysbiosis. The interplay between polysaccharides and gut microbiota may play crucial roles in their anti-obesity effects, but is largely unknown, including the impact of polysaccharides on the composition of the gut microbiota with polysaccharide-degrading capacity. The primary structure of a 5.1 kDa fucan (J2H) from Saccharina japonica was characterized and oral administration of J2H effectively suppressed high-fat diet-induced obesity, blood glucose metabolic dysfunction, dyslipidemia, and gut microbiota dysbiosis. Furthermore, the Jensen-Shannon divergence analysis demonstrated that J2H enriched at least four gut bacterial species with fucoidan-degrading potential, including Bacteroides sartorii and Bacteroides acidifaciens. Our findings suggest that the low molecular weight S. japonica fucan, J2H, is a promising potential agent for obesity prevention and its enrichment of gut bacteria with fucoidan-degrading potential may play a vital role in the anti-obesity effects.

6. Chen Jianwei, Lu Yaojia, Du Yujie, Wang Hong*, Wuqiang*. Recent development of small-molecular inhibitors against Clostridioides difficile infection. Bioorganic Chemistry. 2022. 125: 105843. (https://doi.org/10.1016/j.bioorg.2022.105843) IF: 5.275

Abstract

Clostridioides difficile infection is one of the leading causes of antibiotic-associated infectious diarrhea, and is associated with increased incidence and severity worldwide. While antibiotics have traditionally been used for prophylaxis and treatment of C. difficile infection, elevated antibiotic resistance has promoted the development and spread of C. difficile infection. Since the current standard-of-care antibiotics are ineffective for treating infections, there is an urgent need for novel antibacterial drugs or strategies to target C. difficile infection. C. difficile virulence and vital physiological functions are considered to be ideal targets. Thus, several promising lead compounds have been identified through screening both synthetic and natural product libraries. The goal of this review is to provide an update of the current scientific knowledge of C. difficile infection, focusing on small molecule inhibitors, which can effectively inhibit C. difficile by suppressing virulence or destroying vital physiological structures.

7. Du Aoqi#, Ying Ti-Ti#, Zhou Zhenyi, Yu Wenchao, Hu Gangao, Luo Xian, Ma Man-Jing, Yu Yan-Lei, Wang Hong*, Wei Bin*. Non-ribosomal peptide biosynthetic potential of the nematode symbiont Photorhabdus. Environmental Microbiology Reports. 2022, 14(6): 917-925. (https://doi.org/10.1111/1758-2229.13118) IF: 4.006

Abstract

Photorhabdus, the symbiotic bacteria of Heterorhabditis nematodes, has been reported to possess many non-ribosomal peptide synthetase (NRPS) biosynthesis gene clusters (BGCs). To provide an in-depth assessment of the non-ribosomal peptide biosynthetic potential of Photorhabdus, we compared the distribution of BGCs in 81 Photorhabdus strains, confirming the predominant presence (44.80%) of NRPS BGCs in Photorhabdus. All 990 NRPS BGCs were clustered into 275 gene cluster families (GCFs) and only 13 GCFs could be annotated with known BGCs, suggesting their great diversity and novelty. These NRPS BGCs encoded 351 novel peptides containing more than four amino acids, and 173 of them showed high sequence similarity to known BGCs encoding bioactive peptides, implying the promising potential of Photorhabdus to produce valuable peptides. Sequence similarity networking of adenylation (A-) domains suggested that the substrate specificity of A-domains was not directly correlated with the sequence similarity. The molecular similarity network of predicted metabolite scaffolds of NRPS BGCs and reported peptides from Photorhabdus and a relevant database demonstrated that the non-ribosomal peptide biosynthetic potential of Photorhabdus was largely untapped and revealed the core peptides deserving intensive studies. Our present study provides valuable information for the targeted discovery of novel non-ribosomal peptides from Photorhabdus.

8. Zhi Huang#（本科生）, Zhi-Kun Yang#, Si-Qing Chen#, Jian-Wei Chen, Xiao-Ze Bao, Xin-Yi Ye, Bin Wei, Zi-Ning Cui*, Ya-Sheng Li *, Hong Wang*，Design, synthesis of N9- acyl substituted β-carboline derivatives containing 5-phenyl-2-furan moiety as potent anticancer agents. Results in Chemistry. 2022, 4: 100391.(https://doi.org/10.1016/j.rechem.2022.100391)

Abstract

β-Carbolines are of great interest due to their broad spectrum of biochemical effects and pharmaceutical functions, especially antitumor activity. The N9 position at β-carboline is a modification site for important antitumor activity. Several phenylfuran derivatives displayed significant antitumor activity in our previous work. Here, we designed and preparated a series of novel N9-acyl substituted β-carboline derivatives containing 5-phenyl-2-furan moiety as potent anticancer agents. All newly synthesized compounds and β-carboline were evaluated for antitumor activity on five cancer cells. β-Carboline had only weak antitumor activity, while the introduction of the phenylfuran fragment significantly improved the activity. The primary structure–activity relationship study showed that 4-substituted phenylfuran played a key role in anti-cancer activity and compound 8 displayed superior than Camptothecin in anti-proliferative activity against breast cancer cells MCF-7. Flow cytometry studied revealed that compounds 8 and 15 effectively mediated MCF-7 apoptosis. This study lays a working foundation for the research and development of new broad-spectrum antitumor drugs based on β-carboline and phenylfurans, compound 8 would be great promise as a hit antitumor candidate in the future study.

9. Chen Jianwei, Lu Yaojia, Ye Fei, Zhang Hongfang, Zhou Yonglie, Li Jiangtao, Wu Qiang, Xu Xuewei, Wu Qihao, Wei Bin, Zhang Huawei, Wang Hong*, . A small-molecule inhibitor of the anthranilyl-CoA synthetase PqsA for the treatment of multidrug-resistant Pseudomonas aeruginosa. Microbiology Spectrum. 2022,10(4): e02764-21. (https://doi.org/10.1128/spectrum.02764-21) IF: 9.043

ABSTRACT

One of the challenges associated with the treatment of Pseudomonas aeruginosa infections is the high prevalence of multidrug resistance (MDR). Since conventional antibiotics are ineffective at treating such bacterial infections, innovative antibiotics acting upon novel targets or via mechanisms are urgently required. In this study, we identified a quorum sensing inhibitor (QSI), norharmane, that uniquely shows weak antibacterial activity but strongly inhibits pyocyanin production and biofilm formation of MDR P. aeruginosa. Biophysical experiments and molecular docking studies showed that norharmane competes with anthraniloyl-AMP for anthranilyl-CoA synthetase PqsA of P. aeruginosa at the ligand-binding pocket, which is not exploited by current inhibitors, thereby altering transcription regulatory activity. Moreover, norharmane exhibits synergy with polymyxin B. This synergism exhibits a high killing rate, low probability of resistance selection, and minimal cytotoxicity. Notably, norharmane can effectively boost polymyxin B activity against MDR P. aeruginosa-associated infections in animal models. Together, our findings provide novel insight critical to the design of improved PqsA inhibitors, and an effective combination strategy to overcome multiantibiotic bacterial resistance using conventional antibiotics and QSIs.

10. Suqi Yan, Mingyuan Zeng, Hong Wang, Huawei Zhang*，Micromonospora: A Prolific Source of Bioactive Secondary Metabolites with Therapeutic Potential，Journal of Medicinal Chemistry. 2022, 65, 8735−8771. (https://doi.org/10.1021/acs.jmedchem.2c00626) IF: 8.039

Abstract

Micromonospora, one of the most important actinomycetes genera, is well-known as the treasure trove of bioactive secondary metabolites (SMs). Herein, together with an in-depth genomic analysis of the reported Micromonospora strains, all SMs from this genus are comprehensively summarized, containing structural features, bioactive properties, and mode of actions as well as their biosynthetic and chemical synthesis pathways. The perspective enables a detailed view of Micromonospora-derived SMs, which will enrich the chemical diversity of natural products and inspire new drug discovery in the pharmaceutical industry.

11. Song-Wei Li, Qihao Wu, Heng Xu, Li-Gong Yao, Cheng Luo, Hong Wang, Hao Zhang*, Xu-Wen Li*,  Yue-Wei Guo*, Ocellatuperoxides A–F, Uncommon Anti-Tumoral γ-PyronePeroxides from a Photosynthetic MolluskPlacobranchus ocellatus. Marine Drugs. 2022. 20(10): 590. (https://doi.org/10.3390/md20100590) IF: 5.118

Abstract

Six new pairs of γ-pyrone polypropionate enantiomers with an unusual peroxyl bridge at the side chain, namely (±)-ocellatuperoxides A–F (1–6), were isolated and characterized from the South China Sea photosynthetic mollusk Placobranchus ocellatus. Extensive spectroscopic analysis, single crystal X-ray diffraction analysis, ECD- (electronic circular dichroism) comparison, and TDDFT (time-dependent density functional theory) ECD computation were used to determine the structures and absolute configurations of new compounds. In a cell viability assay, several compounds showed considerable anti-tumoral effects on human non-small cell lung cancer cells A549 with Gefitinib (7.4 μM) and Erlotinib (2.1 μM) as positive controls. Further RNA-sequencing analysis and gene expression evaluation indicated that the anti-tumoral activity of the most effective compound 3 was associated with the regulation of several important genes, such as FGFR1 and HDAC5.

12. Yanlei Yu, Li Fu, Peng He, Ke Xia, Sony Varghese, Jonathan Dordick, Hong Wang*, Fuming Zhang*, Robert J. Linhardt*, Enzymatic synthesis of low molecular weight heparins from N-sulfo heparosan depolymerized by heparanase or heparin lyase. Carbohydrate Polymers. 2022, 295: 119825. (https://doi.org/10.1016/j.carbpol.2022.119825)  IF: 10.723

Abstract

Low-molecular-weight heparin (LMWH) is prepared from the controlled chemical or enzymatic depolymerization of animal sourced heparins. It has been widely used as an anticoagulant. Concerns about the shortcomings of animal-derived heparin and the contamination of supply chain demand biochemical approaches for synthesizing LMWH. In the present study, two LMWHs were enzymatically synthesized from low molecular weight N-sulfated heparosan (LMW-NSH) cleaved by recombinant hydrolase, endo-β-glucuronidase, (HepBp) or heparin lyase III (HepIII), followed by subsequent sulfotransferase modifications. Structural characterization shows that LMWH chains prepared using HepBp had a saturated uronic acid residue at their reducing ends, while chains of LMWH prepared using HepIII had an unsaturated uronic acid residue at their non-reducing end. Both LMWHs had anti-factor Xa and anti-factor IIa activities comparable to enoxaparin. This approach demonstrates that the hydrolase, HepBp, can be used to prepare a new type of LMWH that has no unsaturated uronic acid at its non-reducing end.

13. Quan Xu, Ning Zhao, Jin Liu, Jin-Qian Song, Li-Hua Huang, Hong Wang, Xu-Wen Li*, Tao Pang*, Yue-Wei Guo*, Design, synthesis and in vitro biological evaluation of marine phidianidine derivatives as potential anti-inflammatory agents. Bioorganic & Medicinal Chemistry. 2022, 71: 116936. (https://doi.org/10.1016/j.bmc.2022.116936)  IF: 3.461

Abstract

Phidianidines A and B are novel marine indole alkaloids with various biological activities. Based on their potential anti-inflammatory properties, a series of phidianidine derivatives were designed, synthesized, and tested for their effects on IL-17A production in PMA/ionomycin-stimulated T-cell-lymphoma EL-4 cells. Compounds 9a and 22c exhibited excellent anti-inflammatory activity and low toxicity, with IC50 values of 7.7 μM and 5.3 μM for IL-17A production in PMA/ionomycin-stimulated EL-4 cells, respectively. Further mechanistic study showed that 9a could decrease the STAT3 phosphorylation at Y705 to inhibit IL-17A production in EL-4 cells, indicating its ability of preventing the differentiation of Th17 cells and their possible function. This research may give an insight for the discovery of marine indole alkaloid derived anti-inflammatory drug leads for the treatment of T cell-mediated diseases.

14. Yuanyuan Liu, Meijie Xu, Yuqi Tang, Yilan Shao, Hong Wang, Huawei Zhang*, Genome Features and AntiSMASH Analysis of an EndophyticStrain Fusarium sp. R1. Metabolites. 2022, 12, 521. (https://doi.org/10.3390/metabo12060521) IF: 5.581

Abstract

Endophytic fungi are one of the most prolific sources of functional biomolecules with therapeutic potential. Besides playing an important role in serious plant diseases, Fusarium strains possess the powerful capability to produce a diverse array of bioactive secondary metabolites (SMs). In order to in-depth mine gene clusters for SM biosynthesis of the genus Fusarium, an endophytic strain Fusarium sp. R1 isolated from Rumex madaio Makino was extensively investigated by whole-genome sequencing and in-depth bioinformatic analysis, as well as antiSMASH annotation. The results displayed that strain R1 harbors a total of 51.8 Mb genome, which consists of 542 contigs with an N50 scaffold length of 3.21 Mb and 50.4% GC content. Meanwhile, 19,333 functional protein-coding genes, 338 tRNA and 111 rRNA were comprehensively predicted and highly annotated using various BLAST databases including non-redundant (Nr) protein sequence, nucleotide (Nt) sequence, Swiss-Prot, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG), as well as Pathogen Host Interactions (PHI) and Carbohydrate-Active enzymes (CAZy) databases. Antibiotics and Secondary Metabolites Analysis Shell (AntiSMASH) results showed that strain R1 has 37 SM biosynthetic gene clusters (BGCs), including 17 nonribosomal peptide synthetases (NRPSs), 13 polyketide synthetases (PKSs), 3 terpene synthases (Ts), 3 hybrid NRPS + PKS and 1 hybrid indole + NRPS. These findings improve our knowledge of the molecular biology of the genus Fusarium and would promote the discovery of new bioactive SMs from strain R1 using gene mining strategies including gene knockout and heteroexpression.

16. Jianyun Tao, Xuelian Ba, Mingyuan Zeng, Mengshi Li, Zhe Hu, Yunfen Hua*, Huawei Zhang*, Whole-Genome Sequence Analysis of an Endophytic FungusAlternaria sp. SPS-2 and Its Biosynthetic Potential of BioactiveSecondary Metabolites. Microorganisms. 2022, 10, 1789. (https://doi.org/10.3390/microorganisms10091789) IF: 4.926

Abstract

As one of the commonly isolated endophytic fungi, Alternaria has been known for the production of numerous secondary metabolites (SMs). However, its detailed genomic features and SM biosynthetic potential have not been extensively studied thus far. The present work focuses on the whole-genome sequencing and assembly of an endophytic strain Alternaria sp. SPS-2 derived from Echrysantha chrysantha Lindl. and gene annotation using various bioinformatic tools. The results of this study suggested that the genome of strain SPS-2 was 33.4 Mb in size with a GC content of 51% and an N50 scaffold of 2.6 Mb, and 9789 protein-coding genes, including 644 CAZyme-encoding genes, were discovered in strain SPS-2 through KEGG enrichment analysis. The antiSMASH results indicated that strain SPS-2 harbored 22 SM biosynthetic gene clusters (BGCs), 14 of which are cryptic and unknown. LS–MS/MS and GNPS-based analyses suggested that this endophytic fungus is a potential producer of bioactive SMs and merits further exploration and development.

16. Ping Wang, Shuang Xu, Yuqi Tang, Hong Wang, Xuelian Bai, Huawei Zhang*, Genomic and AntiSMASH Analyses ofMarine-Sponge-Derived Strain Aspergillus niger L14 UnveilingIts Vast Potential of Secondary Metabolites Biosynthesis.  Journal of Fungi. 2022, 8: 591. (https://doi.org/10.3390/jof8060591)  IF: 5.724

Abstract

Aspergillus niger is one of the most important sources of secondary metabolites (SMs), with a wide array of pharmacological effects, including anti-inflammatory, antitumor, immunomodulatory and antioxidant effects. However, the biosynthetic analysis of these bioactive components has been rarely reported owing to the lack of high-quality genome sequences and comprehensive analysis. In this study, the whole genome of one marine-sponge-derived strain A. niger L14 was sequenced and assembled as well as in-depth bioinformatic analysis. The results indicated that the sequence assembly of strain L14 generated one high-quality genome with a total size of 36.1 Mb, a G + C content of 45.3% and an N50 scaffold of 4.2 Mb. Gene annotation was extensively deployed using various BLAST databases, including non-redudant (Nr) protein sequence, nucleotide (Nt) sequence, Swiss-Prot, Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) as well as Pathogen Host Interactions (PHI) and Carbohydrate-active enzymes (CAZy) databases. AntiSMASH analysis revealed that this marine strain harbors a total of 69 SMs biosynthesis gene clusters (BGCs), including 17 PKSs, 18 NRPSs, 21 NRPS-likes, 9 terpenes, 2 indoles, 1 betalactone and 1 siderophore, suggesting its biosynthetic potential to produce a wide variety of SMs. These findings will assist in future investigations on the genetic basis of strain L14 and provide insights into its new bioactive SMs for new drug discovery.

17. FenfenGuo, HongWang*, XinyiYe*, Choon-HongTan, Advanced Synthesis Using Photocatalysis Involved Dual Catalytic System.  European Journal of Organic Chemistry. 2022, 2022(22): e202200326 (1 of 28). (https://doi.org/10.1002/ejoc.202200326)  IF: 3.261

Abstract

Combining visible-light photoredox catalysis with other kinds of catalysis is a powerful strategy to address the barriers met in reactions driven by single catalyst. Under environmentally benign condition, photoredox catalysis produces radical species via visible light irradiation. These species then work with other catalysts, often resulting in unconventional reactivities, by which the scope of reaction could be expanded. Interest focusing on photocatalysis in the synthetic chemistry community has grown tremendously over the past five years, and one of the most striking emerging features is the development of dual catalytic approaches. This minireview summarizes the progress on this theme, mainly including dual catalytic systems merging photoredox activation with acid/base catalysts.

18. Na Lin, Meng-Meng Zhang, Cheng-Shi Jiang, Jia Li, Hong Wang*, Yi-Ran Shen, Yue-Wei Guo*, Uncommon eunicellin-based diterpenoid and 9, 11-secosteroid from theSanya soft coral Cladiella krempfi: Structure and stereochemistry. Tetrahedron Letters. 2022, 95: 153719. (https://doi.org/10.1016/j.tetlet.2022.153719)  IF:2.032

Abstract

Two new compounds, namely an uncommon eunicellin-based diterpenoid (clakrefielin A, 2) and a 9, 11-secosteroid (cladiellasterol A, 4), along with a known carotenoid (all-trans-peridinin, 7), were isolated from the Ximao Island, Sanya Bay soft coral Cladiella krempfi. The structures of these compounds were established on the basis of extensive spectroscopic analysis, X-ray diffraction analysis, chemical transformations, as well as the comparison with the reported data in the literature. The biological activities of these compounds were investigated, and compound 7 was found to be a new protein tyrosine phosphatase 1B (PTP1B) inhibitor (IC50 = 7.2 μM).

19. Jianwei Chen, Siqi Wang, Yiming Xu, Huawei Zhang, Hong Wang*, Anti-TyrosinaseCompoundsfrom the Deep-Sea-Derived Actinomycete Georgenia sp. 40DY180. Chemistry & Biodiversity. 2022,19: e202200037. (https://doi.org/10.1002/cbdv.202200037)  IF: 2.745

Abstract

With the aim of finding new marine-derived skincare promoters, an assay-guided approach was employed to discover tyrosinase-modulating compounds from marine actinomycete. Here we describe a new 2,5-piperazinedione, named georgenione A (1), together with two previously described compounds, 5-(4’-hydroxybenzyl)hydantoin (2) and cyclo(Trp-Gly) (3), produced by actinomycete Georgenia sp. 40DY180, isolated from deep-sea sediments collected in the Pacific Ocean. Their structures were elucidated by a combination of spectroscopic analyses including 1D and 2D NMR and high-resolution mass spectrometric data. 5-(4’-hydroxybenzyl)hydantoin (2) displayed in vitro potent anti-tyrosinase activity with IC50 value of 36 μM, comparable to the commercially used positive control kojic acid (IC50=46 μM) and arbutin (IC50=100 μM). Compounds 1–3 were firstly reported from marine actinomycete Georgenia sp.

20. Yanlei Yu, Li Fu, Peng He, Ke Xia, Sony Varghese, Hong Wang, Fuming Zhang,* Jonathan Dordick,*and Robert J. Linhardt, Chemobiocatalytic Synthesis of a Low-Molecular-Weight Heparin. ACS Chemical Biology. 2022, 17: 637−646. (https://doi.org/10.1021/acschembio.1c00928) IF: 4.634

Abstract

Heparin products are widely used clinical anticoagulants essential in the practice of modern medicine. Low-molecular-weight heparins (LMWHs) are currently prepared by the controlled chemical or enzymatic depolymerization of unfractionated heparins (UFHs) that are extracted from animal tissues. In many clinical applications, LMWHs have displaced UFHs and currently comprise over 60% of the heparin market. In the past, our laboratory has made extensive efforts to prepare bioengineered UFHs relying on a chemoenzymatic process to address concerns about animal-sourced UFHs. The current study describes the use of a novel chemoenzymatic process to prepare a chemobiosynthetic LMWH from a low-molecular-weight heparosan. The resulting chemobiocatalytic LMWH matches most of the United States pharmacopeial specifications for enoxaparin, a LMWH prepared through the base-catalyzed depolymerization of animal-derived UFH.

21. Mengjun Wu,  Dandan Yu, Mingzhi Su, Jianrong Wang, Lei Gong， Zaiyong Zhang， Hong Wang*，Yuewei Guo*, Discovery and photosynthesis of sinuaustones A and B, diterpenoids with a novel carbon scaffold isolated from soft coral Sinularia australiensis from Hainan. Organic Chemistry Frontiers. January 2022. 21(9): 5921-5928. (https://doi.org/10.1039/D2QO01265K) IF: 5.456

Abstract

Two novel diterpenoids, sinuaustones A (1) and B (2), featuring an unprecedented tricyclo[9.3.1.03,15]tetradecane carbon framework, along with a new spatane-type diterpenoid 3 and two related known compounds 4 and 5, were isolated from the South China Sea soft coral Sinularia australiensis. The structures of the new compounds were established by detailed spectroscopic, X-ray diffraction analysis and quantum chemical computation methods. Photosynthesis of 1 and 2 starting from co-isolated 5 was completed giving insight into the plausible biosynthetic pathway of 1 and 2, as well as their structural relationship with co-occurring 3–5. In the in vitro bioassay, compounds 1, 2, 3, and 5 exhibited inhibitory effects on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells with IC50 values of 20.9, 75.1, 9.1, and 30.4 μM, respectively.

22. Bin Wei, Zhen-Yi Zhou, Cong Lai, Ao-Qi Du, Gang-Ao Hu, Wen-Chao Yu, Yan-Lei Yu, Jian-Wei Chen, Hua-Wei Zhang, Qi-Hao Wu, Xue-Wei Xu, Qi Xuan*, Hong Wang*, Predicting the secondary metabolic potential of microbiomes from marker genes using PSMPA. Research Square, September 2022. (https://doi.org/10.21203/rs.3.rs-2036378/v1) This work is licensed under a CC BY 4.0 License. This is a preprint; it has not been peer reviewed by a journal.

Abstract

Background: The efficient discovery of novel antibiotics is of great significance for us to fight against drug-resistant pathogens. Previously, a great deal of time and effort has been spent on screening and isolating novel antibiotic-producing bacteria from complex environmental samples, and the secondary metabolic potential of microbiomes could only be investigated after their genome sequences were available.

Results: Here, we present PSMPA, a web server and a standalone tool, for predicting the numbers of each class of bacterial secondary metabolite biosynthetic gene clusters (BGCs) in environmental samples using 16S rRNA gene amplicons, which could prioritize samples and bacterial strains with high potential to produce novel antibiotics at an early stage. The pipeline integrated PICRUSt2 and BLASTn, and relied on a comprehensive bacterial BGC atlas which contains 1,295,905 BGCs from 216,408 bacterial genomes. PSMPA showed good performance with the accuracy largher than 80% when applied to predict the BGC profiles in 5,000 randomly selected bacterial genomes. Then, PSMPA was applied to depict the distribution of BGCs in microbiomes from human gut, sea water, deep-sea sediments, and soil samples from several independent datasets, which uncovered plenty of novel strains that are rich in BGCs.

Conclusions: We presented a comprehensive bacterial BGC atlas and demonstrated that PSMPA is a usefull tool for predicting the secondary metabolic potential of microbiomes from marker genes. PSMPA would facilitate the efficient discovery of novel microbial secondary metabolites and enrich the resource for amplicon sequencing-based functional analysis. The PSMPA is available at https://www.psmpa.net.

23. Zeng Zirong, Zhang Meng-Meng, Wang Hong, Li Jia, Guo Yue-Wei*, Su Ming-Zhi* . Chemical Constituents of Sinularia nanolobata from the South China Sea. Chinese Journal of Organic Chemistry, 2022, 42, 891-895.  (https://doi.org/10.6023/cjoc202109004)  IF: 6.000

Abstract

A new prenylelemane-type diterpenoid named lobatate (1), together with nine known compounds, namely (17R)-loba-8,10,13(15)-triene-17,18-diol (2), α-tocopherolquinone (3), (1E,3Z,7E,11R,12R)-11-hydroxy-12-methoxy-1-isopropyl4,8,12-trimethyl-cyclotetradeca-1,3,7-triene (4), (＋)-(1E,3E,7E,11R,12S)-11,12-epoxy-11,12-dihydrocembrene-C (5), (1E,3E,7R,8S,11E)-7,8-epoxy-1-isopropyl-4,8,12-trimethyl-cyclotetradeca-1,3,11-triene (6), 24-methylene-cholesterol (7), pregnenolone (8), 3β,6α,11-trihydroxy-24-methylene-9,11-seco-5α-cholest-7-en-9-one (9), sinugrandisterol A (10), was isolated from the soft coral Sinularia nanolobata, which were collected from the Ximao Island, Sanya, South China Sea. Their structures were elucidated using comprehensive spectroscopic methods. The biological activity experiment result showed that compound3 significantly inhibited the enzymatic activity of protein tyrosine phosphatase-1B (PTP1B) with the IC50 value of (4.83±2.35) μmol/L. The result indicated that compound 3 has a promising potential on the drug discovery of anti-diabetes and anti-obesit.