1. Wu Qihao, Ye Fei, Li Xiaolu, Liang Lingfu, Sun Jiadong, Sun Han, Guo Yuewei*, Wang Hong*. Uncommon polyoxygenated sesquiterpenoidsfrom south china sea soft coral Lemnalia flava. Journal of Organic Chemistry, 2019, 84(6), 3083-3092. (https://doi.org/10.1021/acs.joc.8b02912) IF: 4.335

Abstract

A detailed chemical investigation of the Chinese soft coral Lemnalia flava yielded four new nardosinane-type sesquiterpenoids (1–4), one new neolemnane-type sesquiterpenoid (5), and one new sesquiterpenoid with an uncommon 6/9 fused bicyclic skeleton (6), together with two known related compounds (7 and 8). The structures and absolute configurations of 1–8 were determined on the basis of extensive spectroscopic data analyses, X-ray diffraction analysis, chemical reactions, and computer-assisted structural elucidation including 13C NMR data calculation, residual dipolar coupling based NMR analysis, and time-dependent density functional theoryelectronic circular dichroism calculation. Plausible biogenetic pathways of two uncommon sesquiterpenoids (4 and 6) were proposed.

2. Chen Jianwei, Wang Bixia, Lu Yaojia, Guo Yuqi, Sun Jiadong, Wei Bin, Zhang Huawei, Wang Hong*. Quorum sensing inhibitors frommarine microorganisms and their synthetic derivatives. Marine Drugs, 2019, 17(2), 80-107. (https://doi.org/10.3390/md17020080) IF: 4.073

Abstract

Quorum sensing inhibitors (QSIs) present a promising alternative or potent adjuvants of conventional antibiotics for the treatment of antibiotic-resistant bacterial strains, since they could disrupt bacterial pathogenicity without imposing selective pressure involved in antibacterial treatments. This review covers a series of molecules showing quorum sensing (QS) inhibitory activity that are isolated from marine microorganisms, including bacteria, actinomycetes and fungi, and chemically synthesized based on QSIs derived from marine microorganisms. This is the first comprehensive overview of QSIs derived from marine microorganisms and their synthetic analogues with QS inhibitory activity.

3. Pan Rui, Bai Xuelian, Chen Jianwei, Zhang Huawei*, Wang Hong*. Exploringstructural diversity of microbe secondary metabolites usingOSMAC strategy: a literature review. Frontiers in Microbiology, 2019,10, 294. (https://doi.org/10.3389/fmicb.2019.00294) IF: 4.235

Abstract

Microbial secondary metabolites (MSMs) have played and continue to play a highly significant role in the drug discovery and development process. Genetically, MSM chemical structures are biologically synthesized by microbial gene clusters. Recently, however, the speed of new bioactive MSM discovery has been slowing down due to consistent employment of conventional cultivation and isolation procedure. In order to alleviate this challenge, a number of new approaches have been developed. The strategy of one strain many compounds (OSMAC) has been shown as a simple and powerful tool that can activate many silent biogenetic gene clusters in microorganisms to make more natural products. This review highlights important and successful examples using OSMAC approaches, which covers changing medium composition and cultivation status, co-cultivation with other strain(s), adding enzyme inhibitor(s) and MSM biosynthetic precursor(s). Available evidences had shown that variation of cultivation condition is the most effective way to produce more MSMs and facilitate the discovery of new therapeutic agents.

4. Zhong Qiwu#, Wei Bin#, Wang Sijia, Ke Songze, Chen Jianwei, Zhang Huawei, Wang Hong*. The antioxidant activity of polysaccharidesderived from Marine organisms: an overview. Marine Drugs, 2019, 17(12), 674-708. (https://doi.org/10.3390/md17120674) IF: 4.073

Abstract

Marine-derived antioxidant polysaccharides have aroused extensive attention because of their potential nutritional and therapeutic benefits. However, the comprehensive comparison of identified marine-derived antioxidant polysaccharides is still inaccessible, which would facilitate the discovery of more efficient antioxidants from marine organisms. Thus, this review summarizes the sources, chemical composition, structural characteristics, and antioxidant capacity of marine antioxidant polysaccharides, as well as their protective in vivo effects mediated by antioxidative stress reported in the last few years (2013–2019), and especially highlights the dominant role of marine algae as antioxidant polysaccharide source. In addition, the relationships between the chemical composition and structural characteristics of marine antioxidant polysaccharides with their antioxidant capacity were also discussed. The antioxidant activity was found to be determined by multiple factors, including molecular weight, monosaccharide composition, sulfate position and its degree.

5. Chen Jianwei, Guo Yuqi, Lu Yaojia, Wang Bixia, Sun Jiadong, Zhang Huawei, Wang Hong*. Chemistry and biology of siderophores from marine microbes. Marine Drugs, 2019, 17 (10), 562-590. (https://doi.org/10.3390/md17100562) IF: 4.073

Abstract

Microbial siderophores are multidentate Fe(III) chelators used by microbes during siderophore-mediated assimilation. They possess high affinity and selectivity for Fe(III). Among them, marine siderophore-mediated microbial iron uptake allows marine microbes to proliferate and survive in the iron-deficient marine environments. Due to their unique iron(III)-chelating properties, delivery system, structural diversity, and therapeutic potential, marine microbial siderophores have great potential for further development of various drug conjugates for antibiotic-resistant bacteria therapy or as a target for inhibiting siderophore virulence factors to develop novel broad-spectrum antibiotics. This review covers siderophores derived from marine microbes.

6. Jin Weihua, Wu Wanli, Tang Hong, Wei Bin, Wang Hong, Sun Jiadong, Zhang Wenjing*, Zhong Weihong*. Structure analysis and anti-tumorand anti-angiogenic activities of sulfated galactofucan extracted from Sargassum. Marine Drugs, 2019, 17 (1), 52. (https://doi.org/10.3390/md17010052) IF: 4.073

Abstract

Sulfated galactofucan (ST-2) was obtained from Sargassum thunbergii. It was then desulfated to obtain ST-2-DS, and autohydrolyzed and precipitated by ethanol to obtain the supernatant (ST-2-S) and precipitate (ST-2-C). ST-2-C was further fractionated by gel chromatography into two fractions, ST-2-H (high molecular weight) and ST-2-L (low molecular weight). Mass spectrometry (MS) of ST-2-DS was performed to elucidate the backbone of ST-2. It was shown that ST-2-DS contained a backbone of alternating galactopyranose residues (Gal)n (n ≤ 3) and fucopyranose residues (Fuc)n. In addition, ST-2-S was also determined by MS to elucidate the branches of ST-2. It was suggested that sulfated fuco-oligomers might be the branches of ST-2. Compared to the NMR spectra of ST-2-H, the spectra of ST-2-L was more recognizable. It was shown that ST-2-L contain a backbone of (Gal)n and (Fuc)n, sulfated mainly at C4 of Fuc, and interspersed with galactose (the linkages were likely to be 1→2 and 1→6). Therefore, ST-2 might contain a backbone of (Gal)n (n ≤ 3) and (Fuc)n. The sulfation pattern was mainly at C4 of fucopyranose and partially at C4 of galactopyranose, and the branches were mainly sulfated fuco-oligomers. Finally, the anti-tumor and anti-angiogenic activities of ST-2 and its derivates were determined. It was shown that the low molecular-weight sulfated galactofucan, with higher fucose content, had better anti-angiogenic and anti-tumor activities.

7. Wu Qihao, Chen Wenting, Li Songwei, Ye Jianyu, Huan Xiajuan, Gavagnin Margherita, Yao Ligong, Wang Hong, Miao Zehong, Li Xuwen, Guo  Yuewei*. Cytotoxic nitrogenous terpenoids from two south china seaNudibranchs Phyllidiella pustulosa, Phyllidia coelestis, and their sponge-preyAcanthella cavernosa. Marine Drugs, 2019, 17(1), 56. (https://doi.org/10.3390/md17010056) IF: 4.073

Abstract

A detailed chemical investigation of two South China Sea nudibranchs Phyllidiella pustulosa and Phyllidia coelestis, as well as their possible sponge-prey Acanthella cavernosa, led to the isolation of one new nitrogenous cadinane-type sesquiterpenoid xidaoisocyanate A (1), one new naturally occurring nitrogen-containing kalihinane-type diterpenoid bisformamidokalihinol A (16), along with 17 known nitrogenous terpenoids (2–15, 17–19). The structures of all the isolates were elucidated by detailed spectroscopic analysis and by the comparison of their spectroscopic data with those reported in the literature. In addition, the absolute stereochemistry of the previously reported axiriabiline A (5) was determined by X-ray diffraction (XRD) analysis. In a bioassay, the bisabolane-type sesquiterpenoids 8, 10, and 11 exhibited cytotoxicity against several human cancer cell lines.

8. Wu Qihao#, Gao Yuan#, Zhang Mengmeng, Sheng Li, Li Jia, Li Wuwen, Wang Hong*, Guo Yuewei*. New sesquiterpenoids from the South China Sea soft corals Clavulariaviridis and Lemnalia flava. Beilstein Journal of Organic Chemistry, 2019, 15, 695-702. (https://doi.org/10.3762/bjoc.15.64) IF: 2.622

Abstract

A detailed chemical investigation of the South China Sea soft corals Clavularia viridis and Lemnalia flava yielded four new halogenated laurane-type sesquiterpenoids, namely, isobromolaurenisol (1), clalaurenol A (2), ent-laurenisol (3), clalaurenol B (4), and the new aromadendrane-type sesquiterpenoid claaromadendrene (6), together with three known sesquiterpenoids (5, 7, and 8). Their structures were determined by extensive spectroscopic analysis and by comparison with the previously reported analogues. In a bioassay, compounds 1, 2 and 4 exhibited interesting inhibitory activities in vitro against PTP1B and NF-κB.

9. Wu Qihao,Li Heng, Yang Min, Jia Aiqun, Tang Wei, Wang Hong*,Guo Yuewei*. Two new cembrane-type diterpenoids from the xisha soft coralLemnalia flava. Fitoterapia, 2019, 134, 481-484.(http://dx.doi.org/10.1016/j.fitote.2019.03.018) IF: 2.527

Abstract

Further chemical investigation of the South China Sea soft coral Lemnalia flava resulted in the isolation and characterization of two new cembranoids, namely, xishaflavalins G and H (1 and 2), along with three known related compounds (3–5). The structures of the new compounds were elucidated by detailed spectroscopic analysis and by the comparison of their spectroscopic data with those reported in the literature. The discovery of cembrane-type diterpenes from soft coral of the genus Lemnalia was reported for the first time. In addition, compound 5 exhibited moderate inhibitory effects on the ConA-induced T lymphocytes and/or lipopolysaccharide (LPS)-induced B lymphocytes proliferation.

10. Wu Qihao,Li Xuwen, Li Heng, Yao Ligong, Tang Wei, Miao Zehong, Wang Hong*, Guo Yuewei*. Bioactive Polyoxygenated Cembranoids from a Novel HainanChemotype of the Soft Coral Sinularia flexibilis. Bioorganic & Medicinal Chemistry Letters, 2019, 29(2), 185-188. (https://doi.org/10.1016/j.bmcl.2018.12.004 ) IF:2.572

Abstract

Different chemotypes of Sinularia flexibilis exist in the Hainan island. Thus, a collection of this soft coral from a location different from the one of our previous study afforded three novel cembranoid esters featuring a n-butyl alcohol moiety, a structural element rare in natural products of both terrestrial and marine origin. The structures of the new compounds were elucidated by detailed spectroscopic analysis and by the comparison of their spectroscopic data with those reported in the literature. In addition, the absolute stereochemistry of the previously reported diepoxycembrene (9) was first time determined by the X-ray diffraction analysis. In bioassays, compounds 6–8 exhibited strong anti-inflammatory effect with IC50 values of 2.7, 4.7, and 4.2 μM, respectively, whereas compound 5 displayed cytotoxicity against several cancer cells with IC50 values ranging from 8.9 to 27.4 μM. A preliminary structural-activity relationship (SAR) was also described.

11. Wu Qihao, Nay Bastien, Yang Min, Ni Yeke, Wang Hong, Yao Ligong, Li Xuewen*. Marine sponges of the genus Stelletta as promising drug sources:chemical and biological aspects. Acta Pharmaceutica Sinica B, 2019, 9(2), 237-257. (https://doi.org/10.1016/j.apsb.2018.10.003) IF: 7.097

Abstract

Marine sponges of the genus Stelletta are well known as rich sources of diverse and complex biologically relevant natural products, including alkaloids, terpenoids, peptides, lipids, and steroids. Some of these metabolites, with novel structures and promising biological activities, have attracted a lot of attention from chemists seeking to perform their total synthesis in parallel to intensive biological studies towards new drug leads. In this review, we summarized the distribution of the chemically investigated Stelletta sponges, the isolation, synthesis and biological activities of their secondary metabolites, covering the literature from 1982 to early 2018.

12. Liu Pengfu,Chen Yan, Shao Zongze, Chen Jianwei, Wu Jiequn, Guo Qian, Shi  Jiping, Wang Hong*, Chu Xiaohe*. AhlX, an N-acylhomoserine Lactonase with Unique Properties. Marine Drugs, 2019, 17, 387-401. (http://dx.doi.org/10.3390/md17070387) IF: 4.073

Abstract

N-Acylhomoserine lactonase degrades the lactone ring of N-acylhomoserine lactones (AHLs) and has been widely suggested as a promising candidate for use in bacterial disease control. While a number of AHL lactonases have been characterized, none of them has been developed as a commercially available enzymatic product for in vitro AHL quenching due to their low stability. In this study, a highly stable AHL lactonase (AhlX) was identified and isolated from the marine bacterium Salinicola salaria MCCC1A01339. AhlX is encoded by a 768-bp gene and has a predicted molecular mass of 29 kDa. The enzyme retained approximately 97% activity after incubating at 25 °C for 12 days and ~100% activity after incubating at 60 °C for 2 h. Furthermore, AhlX exhibited a high salt tolerance, retaining approximately 60% of its activity observed in the presence of 25% NaCl. In addition, an AhlX powder made by an industrial spray-drying process attenuated Erwinia carotovora infection. These results suggest that AhlX has great potential for use as an in vitro preventive and therapeutic agent for bacterial diseases.

13. Shi Yutong, Pan Chengqian, Cen Suoyu, Fu Leilei, Cao Xun, Wang Hong, Wang Kuiwu, Wu Bin*. Comparative metabolomics reveals defence-relatedmodification of citrinin by Penicillium citrinum within a syntheticPenicillium-Pseudomonas community. Environmental Microbiology, 2019, 21(1), 496-510. (https://doi.org/10.1111/1462-2920.14482) IF: 4.933

Abstract

Co-occurring microorganisms have been proved to influence the performance of each other by metabolic means in nature. Here we generated a synthetic fungal-bacterial community comprising Penicillium citrinum and Pseudomonas aeruginosa employing the previously described membrane-separated co-culture device. By applying a newly designed molecular networking routine, new citrinin-related metabolites induced by the fungal-bacterial cross-talk were unveiled in trace amounts. A mechanically cycled co-culture setup with external pumping forces accelerating the chemically interspecies communication was then developed to boost the production of cross-talk-induced metabolites. Multivariate data analysis combined with molecular networking revealed the accumulation of a pair of co-culture-induced molecules whose productions were positively correlated to the exchange rate in the new co-cultures, facilitating the discovery of the previously undescribed antibiotic citrinolide with a novel skeleton. This highly oxidized citrinin adduct showed significantly enhanced antibiotic property against the partner strain P. aeruginosa than its precursor citrinin, suggesting a role in the microbial competition. Thus, we propose competitive-advantage-oriented structural modification driven by microbial defence response mechanism in the interspecies cross-talk might be a promising approach in the search for novel antibiotics. Besides, this study highlights the utility of MS-based metabolomics as an effective tool in the direct biochemical analysis of the community metabolism.

14. Yan Zhixiang, Li Ting, Wei Bin, Wang Panpan, Wan Jianbo, Wang Yitao, Yan Ru*. High-resolution MS/MS metabolomics by data-independent acquisition revealsurinary metabolic alteration in experimental colitis. Metabolomics, 2019, 15, 70-80. (https://doi.org/10.1007/s11306-019-1534-1) IF: 2.881

Abstract

Introduction: Traditional high-resolution MS1 based untargeted metabolomics suffers from low sensitivity, while low-resolution MS/MS based multiple reaction monitoring increases sensitivity at the cost of metabolite coverage and the mass accuracy.

Objectives: To evaluate and apply the high-resolution MS/MS level untargeted metabolomics.

Methods: SWATH based data-independent acquisition (DIA) was optimized to obtain MS/MS of all precursor ions.

Results: SWATH-MS/MS could rescue MS1 obscured or saturated metabolites and potentially provide diagnostic fragments to differentiate isomers. For SWATH-MS/MS, 4944 out of 21492 (23.0%) and 2289 out of 12831 (17.8%) fragment ion features significantly changed (Fold change > 1.5, P < 0.05) between Normal and experimental acute ulcerative colitis (UC) groups in positive and negative ion mode, respectively. For SWATH-MS1, 1022 out of 4818 (21.2%) and 353 out of 2266 (15.6%) features significantly changed in positive and negative ion mode, respectively. By deciphering the metabolite profiles with high-resolution MS/MS, it allows versatile post-acquisition data mining such as open detection of different sub-metabolome. The method revealed a global urinary metabolic alteration and increased glucuronide and sulfate sub-metabolome in UC. The major limitation of untargeted SWATH-MS/MS is increased interferences derived from wider Q1 isolation window.

Conclusions: SWATH-MS/MS is a versatile metabolomics strategy, merging the coverage of high-resolution untargeted metabolomics and the sensitivity of MS/MS.