128 results on '"Yiguang Zhu"'
Search Results
2. Flavin-enabled reductive and oxidative epoxide ring opening reactions
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Bidhan Chandra De, Wenjun Zhang, Chunfang Yang, Attila Mándi, Chunshuai Huang, Liping Zhang, Wei Liu, Mark W. Ruszczycky, Yiguang Zhu, Ming Ma, Ghader Bashiri, Tibor Kurtán, Hung-wen Liu, and Changsheng Zhang
- Subjects
Science - Abstract
Epoxide ring opening reactions are important in both biological processes and synthetic applications. Here, the authors show that flavin cofactors can catalyze reductive and oxidative epoxide ring opening reactions and propose the underlying mechanisms.
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- 2022
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3. Genomics-Driven Discovery of Benzoxazole Alkaloids from the Marine-Derived Micromonospora sp. SCSIO 07395
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Ziqian Cheng, Qingbo Zhang, Jing Peng, Xiaoyang Zhao, Liang Ma, Changsheng Zhang, and Yiguang Zhu
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benzoxazole alkaloids ,genome mining ,heterologous expression ,Micromonospora sp. ,marine natural products ,Organic chemistry ,QD241-441 - Abstract
Benzoxazole alkaloids exhibit a diverse array of structures and interesting biological activities. Herein we report the identification of a benzoxazole alkaloid-encoding biosynthetic gene cluster (mich BGC) in the marine-derived actinomycete Micromonospora sp. SCSIO 07395 and the heterologous expression of this BGC in Streptomyces albus. This approach led to the discovery of five new benzoxazole alkaloids microechmycin A–E (1–5), and a previously synthesized compound 6. Their structures were elucidated by HRESIMS and 1D and 2D NMR data. Microechmycin A (1) showed moderate antibacterial activity against Micrococcus luteus SCSIO ML01 with the minimal inhibitory concentration (MIC) value of 8 μg mL−1.
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- 2023
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4. Molecular basis of dimer formation during the biosynthesis of benzofluorene-containing atypical angucyclines
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Chunshuai Huang, Chunfang Yang, Wenjun Zhang, Liping Zhang, Bidhan Chandra De, Yiguang Zhu, Xiaodong Jiang, Chunyan Fang, Qingbo Zhang, Cheng-Shan Yuan, Hung-wen Liu, and Changsheng Zhang
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Science - Abstract
Benzofluorene-containing angucyclines, bacterial natural compounds with potential use as therapeutics/antibiotics, occur as dimers. Here, the authors elucidated the dimerization mechanism which turned out to work spontaneously, without enzymatic catalysis.
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- 2018
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5. Marine Bacterial Aromatic Polyketides From Host-Dependent Heterologous Expression and Fungal Mode of Cyclization
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Chunshuai Huang, Chunfang Yang, Yiguang Zhu, Wenjun Zhang, Chengshan Yuan, and Changsheng Zhang
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heterologous expression ,aromatic polyketides ,type II polyketide synthase ,cyclization modes ,pathway crosstalk ,Chemistry ,QD1-999 - Abstract
The structure diversity of type II polyketide synthases-derived bacterial aromatic polyketides is often enhanced by enzyme controlled or spontaneous cyclizations. Here we report the discovery of bacterial aromatic polyketides generated from 5 different cyclization modes and pathway crosstalk between the host and the heterologous fluostatin biosynthetic gene cluster derived from a marine bacterium. The discovery of new compound SEK43F (2) represents an unusual carbon skeleton resulting from a pathway crosstalk, in which a pyrrole-like moiety derived from the host Streptomyces albus J1074 is fused to an aromatic polyketide SEK43 generated from the heterologous fluostatin type II PKSs. The occurrence of a new congener, fluoquinone (3), highlights a bacterial aromatic polyketide that is exceptionally derived from a characteristic fungal F-mode first-ring cyclization. This study expands our knowledge on the power of bacterial type II PKSs in diversifying aromatic polyketides.
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- 2018
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6. Discovery of Stealthin Derivatives and Implication of the Amidotransferase FlsN3 in the Biosynthesis of Nitrogen-Containing Fluostatins
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Chunshuai Huang, Chunfang Yang, Zhuangjie Fang, Liping Zhang, Wenjun Zhang, Yiguang Zhu, and Changsheng Zhang
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angucyclines ,N–N bond ,raceme ,gene inactivation ,biosynthesis ,marine ,Micromonospora ,Biology (General) ,QH301-705.5 - Abstract
Diazobenzofluorene-containing atypical angucyclines exhibit promising biological activities. Here we report the inactivation of an amidotransferase-encoding gene flsN3 in Micromonospora rosaria SCSIO N160, a producer of fluostatins. Bioinformatics analysis indicated that FlsN3 was involved in the diazo formation. Chemical investigation of the flsN3-inactivation mutant resulted in the isolation of a variety of angucycline aromatic polyketides, including four racemic aminobenzo[b]fluorenes stealthins D–G (9–12) harboring a stealthin C-like core skeleton with an acetone or butanone-like side chain. Their structures were elucidated on the basis of nuclear magnetic resonance (NMR) spectroscopic data and X-ray diffraction analysis. A plausible mechanism for the formation of stealthins D–G (9–12) was proposed. These results suggested a functional role of FlsN3 in the formation/modification of N–N bond-containing fluostatins.
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- 2019
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7. Biosynthesis and Engineered Overproduction of Everninomicins with Promising Activity against Multidrug-Resistant Bacteria
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Mengyi Zhu, Lijuan Wang, Haibo Zhang, Liping Zhang, Bin Tan, Qi Huang, Yiguang Zhu, and Changsheng Zhang
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Biomedical Engineering ,General Medicine ,Biochemistry, Genetics and Molecular Biology (miscellaneous) - Published
- 2023
8. Biosynthetic Diversification of Fidaxomicin Aglycones by Heterologous Expression and Promoter Refactoring
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Lijuan Wang, Mengyi Zhu, Qingbo Zhang, Shilan Zhai, Yiguang Zhu, Haibo Zhang, and Changsheng Zhang
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Pharmacology ,Complementary and alternative medicine ,Organic Chemistry ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine ,Analytical Chemistry - Published
- 2023
9. Characterization of the <scp>P450</scp> Monooxygenase <scp>LobP1</scp> as C‐32 Hydroxylase in Lobophorin Biosynthesis
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Bin Tan, Qingbo Zhang, Ji Xiao, Chengshan Yuan, Yuchan Chen, Siqiang Chen, Weimin Zhang, Yiguang Zhu, and Changsheng Zhang
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General Chemistry - Published
- 2023
10. Aromatic Polyketides from the Mangrove-Derived Streptomyces sp. SCSIO 40069
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Lili Sun, Hanning Zhu, Liping Zhang, Yiguang Zhu, Disna Ratnasekera, Changsheng Zhang, and Qingbo Zhang
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Pharmacology ,Complementary and alternative medicine ,Organic Chemistry ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine ,Analytical Chemistry - Published
- 2023
11. Discovery of Efrotomycin Congeners and Heterologous Expression-Based Insights into the Self-Resistance Mechanism
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Chunyan Fang, Qingbo Zhang, Wenjun Zhang, Changsheng Zhang, and Yiguang Zhu
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Pharmacology ,Complementary and alternative medicine ,Organic Chemistry ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine ,Analytical Chemistry - Abstract
Four new efrotomycins, A1-A4 (
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- 2022
12. A Widespread Glycosidase Confers Lobophorin Resistance and Host‐Dependent Structural Diversity
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Bin Tan, Liping Zhang, Qingbo Zhang, Siqiang Chen, Weiliang Xiong, Yiguang Zhu, and Changsheng Zhang
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General Medicine ,General Chemistry ,Catalysis - Published
- 2023
13. Antifungal Macrolides Kongjuemycins from Coral-Associated Rare Actinomycete Pseudonocardia kongjuensis SCSIO 11457
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Zhuangjie Fang, Qingbo Zhang, Liping Zhang, Jianglian She, Jie Li, Wenjun Zhang, Haibo Zhang, Yiguang Zhu, and Changsheng Zhang
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Organic Chemistry ,Physical and Theoretical Chemistry ,Biochemistry - Published
- 2022
14. Characterization of the P450 Monooxygenase LobP1 as C-32 Hydroxylase in Lobophorin Biosynthesis
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Bin Tan, Qingbo Zhang, Ji Xiao, Cheng-shan Yuan, Yuchan Chen, Siqiang Chen, Weimin Zhang, Yiguang Zhu, and Changsheng Zhang
- Abstract
Lobophorins (LOBs) belong to a large family of spirotetronate antibiotics with antibacterial and antitumor activities. In this study, we demonstrated the function of LobP1, a P450 monooxygenase encoded in the LOB biosynthetic gene cluster, by in vivo deletion and in vitro biochemical assays. The disruption of lobP1 led to the isolation of three new LOBs derivatives (3‒5) and three known ones (6‒8) without the hydroxyl group at C-32. LobP1 was shown to have relatively broad substrate scope. Determing the kinetic parameters of LobP1 towards different substrates revealed that LobP1 preferred substrate with a nitrosugar. The major product LOB E (6) from the ∆lobP1 mutant displayed better cytotoxic activities against several cancer cell lines than LOB B, the C-32 hydroxlated counterpart.
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- 2023
15. Totopotensamide Congeners from a Halogenase-Inactivated Mutant
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Bin Tan, Qingbo Zhang, Jieyi Li, Yiguang Zhu, Liping Zhang, Wenjun Zhang, Haibo Zhang, Yang Chen, and Changsheng Zhang
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Pharmacology ,Complementary and alternative medicine ,Organic Chemistry ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine ,Analytical Chemistry - Abstract
The installation of halogen atoms into aromatic and less activated polyketide substrates by halogenases is a powerful strategy to tune the bioactivity, bioavailability, and reactivity of compounds. In the biosynthetic pathway of totopotensamide A (
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- 2023
16. A simple and facile iodination method of didechlorotiacumicin B and aromatic compounds
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Haibo Zhang, Li-Ping Zhang, Imran Khan, Yiguang Zhu, Guangtao Zhang, and Changsheng Zhang
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Metal free ,Chemistry ,Chlorine atom ,Halide ,Halogenation ,Tiacumicin B ,General Chemistry ,Ring (chemistry) ,Combinatorial chemistry ,Clostridium difficile infections - Abstract
Tiacumicin B (also known as fidaxomicin or difimicin) is a marketed 18-membered macrolide antibiotic for the treatment of Clostridium difficile infections. Tiacumicin B is structurally characterized with two chlorine atoms substituted on the aromatic ring, which is installed by the halogenase TiaM. During the study on halide compatibility of TiaM, a facile and nonenzymatic iodination method of didechlorotiacumicin B was discovered, requiring NaI, acid and air for iodination at room temperature. This method was also amenable to other 9 aromatic substrates with electron-rich sites for iodination.
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- 2021
17. Discovery of an Unexpected 1,4-Oxazepine-Linked seco-Fluostatin Heterodimer by Inactivation of the Oxidoreductase-Encoding Gene flsP
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Li-Ping Zhang, Yiguang Zhu, Chun-Shuai Huang, Wenjun Zhang, Changsheng Zhang, and Chunfang Yang
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Pharmacology ,chemistry.chemical_classification ,Stereochemistry ,Organic Chemistry ,Absolute configuration ,Pharmaceutical Science ,Structural diversity ,Flavin group ,Fluorene ,Ring (chemistry) ,Analytical Chemistry ,chemistry.chemical_compound ,Complementary and alternative medicine ,chemistry ,Oxidoreductase ,Drug Discovery ,Molecular Medicine ,Oxazepine ,Gene - Abstract
Fluostatins belong to the atypical angucyclinone aromatic polyketides featuring a distinctive tetracyclic benzo[a]fluorene skeleton. To understand the formation of the heavily oxidized A-ring in fluostatins, a flavin adenine dinucleotide-binding oxidoreductase-encoding gene flsP was inactivated, leading to the production of an unprecedented 1,4-oxazepine-linked seco-fluostatin heterodimer difluostatin I (7) and five new fluostatin-related derivatives, fluostatins T-X (8-12). Their structures were elucidated by mass spectrometry, nuclear magnetic resonance, X-ray diffraction analysis, and biosynthetic considerations. Difluostatin I (7) represents the first example with an A-ring-cleaved 3',4'-seco-fluostatin skeleton. The absolute configuration of fluostatin T (8) was determined by X-ray diffraction analysis. Fluostatin W (11) contains an uncommon isoxazolinone ring. These findings highlight the structural diversity of fluostatins.
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- 2021
18. New piericidin derivatives from the marine-derived streptomyces sp. SCSIO 40063 with cytotoxic activity
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Xiaodong Jiang, Yiguang Zhu, Jing Peng, Changsheng Zhang, Liang Ma, Ting Long, Ziqian Cheng, and Qingbo Zhang
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biology ,010405 organic chemistry ,Stereochemistry ,Chemistry ,Organic Chemistry ,Plant Science ,biology.organism_classification ,01 natural sciences ,Biochemistry ,Nmr data ,Streptomyces ,0104 chemical sciences ,Analytical Chemistry ,Human tumor ,010404 medicinal & biomolecular chemistry ,Cell culture ,Ic50 values ,Cytotoxic T cell - Abstract
Two new piericidins A5 (1) and G1 (2), a previously synthesized piericidin G2 (3), and two known piericidins A1 (4) and A2 (5) were isolated from the marine-derived Streptomyces sp. SCSIO 40063. The structures of 1-5 were elucidated by HRESIMS, 1 D, 2 D NMR data analyses and comparisons with the known compounds. Compound 2 showed moderate cytotoxicities against four human tumor cell lines SF-268, MCF-7, HepG2 and A549 with IC50 values between 10.0 and 12.7 μM.
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- 2021
19. Genome mining of cryptic tetronate natural products from a PKS-NRPS encoding gene cluster in Trichoderma harzianum t-22
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Junfeng Wang, Mengbin Chen, Yiguang Zhu, Yan Yan, Pengyun Mou, and Yi Tang
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biology ,Chemistry ,Organic Chemistry ,food and beverages ,Trichoderma harzianum ,biology.organism_classification ,Biochemistry ,Small molecule ,Polyketide ,Aspergillus nidulans ,Dioxygenase ,Gene cluster ,Physical and Theoretical Chemistry ,Gene ,Oxidative decarboxylation - Abstract
Trichoderma harzianum is a widely used biocontrol agent in agriculture. Obtaining a full inventory of the small molecules that can be biosynthesized from the encoded biosynthetic gene clusters (BGCs) is therefore useful for understanding associated plant-microbe and microbe-microbe interactions. Here we heterologously reconstituted a polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) encoding gene cluster from T. harzianum t-22 in Aspergillus nidulans A1145. Six new tetronate natural products trihazone A-F (1-6) were isolated and elucidated by HRESIMS and 1D and 2D NMR data. Three of the products contain an exocyclic olefin, which is derived from the oxidative decarboxylation of an α-ketoglutarate-dependent dioxygenase ThnC as shown by biochemical assays.
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- 2021
20. A new xanthostatin analogue from the marine sponge-associated actinomycete Streptomyces sp. SCSIO 40064
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Xinya Zhang, Xiaodong Jiang, Haibo Zhang, Changsheng Zhang, Yiguang Zhu, Siqiang Chen, Li-Ping Zhang, and Qingbo Zhang
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biology ,010405 organic chemistry ,Chemistry ,Stereochemistry ,Organic Chemistry ,Absolute configuration ,Plant Science ,biology.organism_classification ,01 natural sciences ,Biochemistry ,Streptomyces ,0104 chemical sciences ,Analytical Chemistry ,010404 medicinal & biomolecular chemistry ,Sponge - Abstract
A new cyclo-heptadepsipeptide xanthostatin B (1), together with isobutyryl hexapeptide (2), xanthostatin (3), TXS-1 (4) and TXS-2 (5), were isolated from the marine sponge derived Streptomyces sp. SCSIO 40064. The structures were elucidated by comprehensive spectroscopic data analyses and comparison with the literatures. The D-Val unit in 1 was assigned by Marfey's method. The absolute configuration of 4 was determined by X-ray crystallographic analysis. Compounds 1‒5 were evaluated for the inhibitory activities against four pharmaceutical targets and six antibacterial indicator strains. Compound 5 displayed α-glucosidase inhibitory activity with IC50 value of 18.67 ± 1.27 µM.
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- 2020
21. Mutation of an atypical oxirane oxyanion hole improves regioselectivity of the α/β-fold epoxide hydrolase Alp1U
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Attila Mándi, Bidhan Chandra De, Yiguang Zhu, Zhuangjie Fang, Changsheng Zhang, Li-Ping Zhang, Wenjun Zhang, Chunfang Yang, and Tibor Kurtán
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Ethylene Oxide ,0301 basic medicine ,Stereochemistry ,Diol ,Epoxide ,Crystallography, X-Ray ,Biochemistry ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,Nucleophile ,Epoxide hydrolase ,Molecular Biology ,Epoxide Hydrolases ,Sequence Homology, Amino Acid ,030102 biochemistry & molecular biology ,Chemistry ,Hydrolysis ,Regioselectivity ,Stereoisomerism ,Cell Biology ,Streptomyces ,Enzyme structure ,Protein Structure, Tertiary ,Kinetics ,030104 developmental biology ,Mutation ,Mutagenesis, Site-Directed ,Enzymology ,Epoxy Compounds ,Oxyanion hole - Abstract
Epoxide hydrolases (EHs) have been characterized and engineered as biocatalysts that convert epoxides to valuable chiral vicinal diol precursors of drugs and bioactive compounds. Nonetheless, the regioselectivity control of the epoxide ring opening by EHs remains challenging. Alp1U is an α/β-fold EH that exhibits poor regioselectivity in the epoxide hydrolysis of fluostatin C (compound 1) and produces a pair of stereoisomers. Herein, we established the absolute configuration of the two stereoisomeric products and determined the crystal structure of Alp1U. A Trp-186/Trp-187/Tyr-247 oxirane oxygen hole was identified in Alp1U that replaced the canonical Tyr/Tyr pair in α/β-EHs. Mutation of residues in the atypical oxirane oxygen hole of Alp1U improved the regioselectivity for epoxide hydrolysis on 1. The single site Y247F mutation led to highly regioselective (98%) attack at C-3 of 1, whereas the double mutation W187F/Y247F resulted in regioselective (94%) nucleophilic attack at C-2. Furthermore, single-crystal X-ray structures of the two regioselective Alp1U variants in complex with 1 were determined. These findings allowed insights into the reaction details of Alp1U and provided a new approach for engineering regioselective epoxide hydrolases.
- Published
- 2020
22. S-Bridged Thioether and Structure-Diversified Angucyclinone Derivatives from the South China Sea-Derived Micromonospora echinospora SCSIO 04089
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Wenjun Zhang, Haibo Zhang, Li-Ping Zhang, Xiaodong Jiang, Zhuangjie Fang, Yiguang Zhu, Changsheng Zhang, Chunfang Yang, and Qingbo Zhang
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Pharmacology ,Anthracene ,South china ,biology ,010405 organic chemistry ,Stereochemistry ,Organic Chemistry ,Pharmaceutical Science ,Fluorene ,biology.organism_classification ,01 natural sciences ,Naphthoquinone ,0104 chemical sciences ,Analytical Chemistry ,Angucyclinone ,Micromonospora echinospora ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,Complementary and alternative medicine ,chemistry ,Thioether ,Drug Discovery ,Molecular Medicine ,Benzofuran - Abstract
Angucyclinces belong to the class of aromatic polyketides and display a wide variety of structure diversity and pharmaceutical significance. Herein we report the isolation, structure elucidation, and bioactivity evaluation of structure-diversified angucyclinone derivatives and anthracene from the South China Sea-derived Micromonospora echinospora SCSIO 04089, including a thioether, gephysulfuromycin (1), two new benzo[b]phenanthridines, homophenanthroviridone (2) and homophenanthridonamide (3), a new benzo[b]fluorene, homostealthin D (4), a new naphtho[2,3-b]benzofuran, nenesfuran (5), a new naphthoquinone, WS-5995 D (6) and a new anthracene, nenesophanol (7), together with three known compounds (8-10). Their structures were elucidated by extensive spectroscopic analyses. The structures of 1-3 and 5-8 were confirmed by X-ray crystallographic analyses. Gephysulfuromycin (1) featured a rare single S-bridged 3,12a-epithiotetraphene skeleton. Homophenanthroviridone (2) was found to be cytotoxic to SF-268, MCF-7, and HepG2 cell lines with IC50 values of 5.4 ± 0.4, 6.8 ± 0.3, and 1.4 ± 0.1 μM, respectively. Compound 2 was also active against Gram-positive bacteria with MIC (minimal inhibition concentration) values ranging 2-4 μg mL-1.
- Published
- 2020
23. Refactoring the Concise Biosynthetic Pathway of Cyanogramide Unveils Spirooxindole Formation Catalyzed by a P450 Enzyme
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Li-Ping Zhang, Shilan Zhai, Weiming Zhu, Zhiwen Liu, Yiguang Zhu, Jing Peng, Qingbo Zhang, Liang Ma, Yingli Zhang, Chunyan Fang, and Changsheng Zhang
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Methyltransferase ,Enzyme catalyzed ,computer.software_genre ,Crystallography, X-Ray ,010402 general chemistry ,01 natural sciences ,Catalysis ,Indole Alkaloids ,chemistry.chemical_compound ,Cytochrome P-450 Enzyme System ,Biosynthesis ,Cyanogramide ,Gene cluster ,Rearrangement reaction ,chemistry.chemical_classification ,Molecular Structure ,biology ,010405 organic chemistry ,Streptomyces coelicolor ,General Medicine ,General Chemistry ,Monooxygenase ,biology.organism_classification ,Biosynthetic Pathways ,Oxindoles ,0104 chemical sciences ,Actinobacteria ,Enzyme ,Code refactoring ,Biochemistry ,chemistry ,Heterologous expression ,computer - Abstract
Cyanogramide (1) from the marine actinomycete Actinoalloteichus cyanogriseus WH1-2216-6 features a unique spirooxindole skeleton and exhibits significant bioactivity to efficiently reverse drug resistance in tumor cells. The biosynthetic gene cluster of 1 in A. cyanogriseus WH1-2216-6 was identified and refactored by promoter engineering for heterologous expression in Streptomyces coelicolor YF11, thereby enabling the production of 1 and five new derivatives. Interesting, four of them, including 1, were identified as enantiomeric mixtures in different ratios. The functions of tailoring enzymes, including two methyltransferases (CyaEF), and three cytochrome P450 monooxygenases (CyaGHI) were confirmed by gene inactivation and feeding experiments, leading to the elucidation of a concise biosynthetic pathway for 1. Notably, CyaH was biochemically verified to catalyze the formation of the spirooxindole skeleton in 1 through an unusual carbocation-mediated semipinacol-type rearrangement reaction.
- Published
- 2020
24. Proximicins F and G and Diproximicin A: Aminofurans from the Marine-Derived Verrucosispora sp. SCSIO 40062 by Overexpression of PPtase Genes
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Li-Ping Zhang, Chunyan Fang, Changsheng Zhang, Yiguang Zhu, Liang Ma, Haibo Zhang, Qingbo Zhang, and Wenjun Zhang
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Pharmacology ,Proximicin B ,biology ,Stereochemistry ,Dimer ,Electrospray ionization ,Organic Chemistry ,Verrucosispora sp ,Pharmaceutical Science ,Bacillus subtilis ,medicine.disease_cause ,biology.organism_classification ,Analytical Chemistry ,chemistry.chemical_compound ,Complementary and alternative medicine ,chemistry ,Staphylococcus aureus ,Drug Discovery ,medicine ,Phosphopantetheinyl transferase ,Molecular Medicine ,Gene - Abstract
Overexpression of phosphopantetheinyl transferase (PPtase)-encoding genes sfp and svp in the marine-derived Verrucosispora sp. SCSIO 40062 led to the production of two new aminofuran monomers, proximicin F (1) and proximicin G (3) and a new dimer diproximicin A (2), along with two known compounds, proximicins B (4) and C (5). Their structures were unambiguously elucidated on the basis of detailed NMR spectroscopic analysis and high-resolution electrospray ionization mass spectrometry (HRESIMS) data. Proximicin B (4) showed moderate antibacterial activities against Staphylococcus aureus, methicillin-resistant S. aureus, and Bacillus subtilis.
- Published
- 2020
25. Deciphering Biosynthetic Enzymes Leading to 4-Chloro-6-Methyl-5,7-Dihydroxyphenylglycine, a Non-Proteinogenic Amino Acid in Totopotensamides
- Author
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Qingbo Zhang, Changsheng Zhang, Siqiang Chen, Li-Ping Zhang, Bin Tan, Yiguang Zhu, and Hongbo Jin
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0301 basic medicine ,Mutant ,Streptomyces pactum ,Methylation ,Peptides, Cyclic ,01 natural sciences ,Biochemistry ,Methoxyhydroxyphenylglycol ,03 medical and health sciences ,chemistry.chemical_compound ,Biosynthesis ,Gene cluster ,Glycosides ,Sulfhydryl Compounds ,Amino Acids ,Transaminases ,Recombination, Genetic ,chemistry.chemical_classification ,Proteinogenic amino acid ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Hydrolysis ,Methyltransferases ,General Medicine ,0104 chemical sciences ,Amino acid ,030104 developmental biology ,Enzyme ,Gene Expression Regulation ,Multigene Family ,Mutation ,Molecular Medicine ,Streptomyces lividans ,Heterologous expression - Abstract
Totopotensamide A (TPM A, 1) is a polyketide-peptide glycoside featuring a nonproteinogenic amino acid 4-chloro-6-methyl-5,7-dihydroxyphenylglycine (ClMeDPG). The biosynthetic gene cluster (BGC) of totopotensamides (tot) was previously activated by manipulating transcription regulators in marine-derived Streptomyces pactum SCSIO 02999. Herein, we report the heterologous expression of the tot BGC in Streptomyces lividans TK64, and the production improvement of TPM A via in-frame deletion of two negative regulators totR5 and totR3. The formation of ClMeDPG was proposed to require six enzymes, including four enzymes TotC1C2C3C4 for 3,5-dihydroxyphenylglycine (DPG) biosynthesis and two modifying enzymes TotH (halogenase) and TotM (methyltransferase). Heterologous expression of the four-gene cassette totC1C2C3C4 led to production of 3,5-dihydroxyphenylglyoxylate (DPGX). The aminotransferase TotC4 was biochemically characterized to convert DPGX to S-DPG. Inactivation of totH led to a mutant accumulated a deschloro derivative TPM H1, and the ΔtotHi/ΔtotMi double mutant afforded two deschloro-desmethyl products TPMs HM1 and HM2. A hydrolysis experiment demonstrated that the DPG moiety in TPM HM2 was S-DPG, consistent with that of the TotC4 enzymatic product. These results confirmed that TotH and TotM were responsible for ClMeDPG biosynthesis. Bioinformatics analysis indicated that both TotH and TotM might act on thiolation domain-tethered substrates. This study provided evidence for deciphering enzymes leading to ClMeDPG in TPM A, and unambiguously determined its absolute configuration as S.
- Published
- 2020
26. Heterologous Expression Leads to Discovery of Diversified Lobophorin Analogues and a Flexible Glycosyltransferase
- Author
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Siqiang Chen, Qingbo Zhang, Changsheng Zhang, Imran Khan, Yiguang Zhu, Yuchan Chen, Bin Tan, and Weimin Zhang
- Subjects
Staphylococcus aureus ,Streptomyces pactum ,Microbial Sensitivity Tests ,Computational biology ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Micrococcus ,Drug Discovery ,Glycosyltransferase ,Gene cluster ,Physical and Theoretical Chemistry ,Molecular Structure ,biology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Glycosyltransferases ,Stereoisomerism ,Streptomyces ,Anti-Bacterial Agents ,0104 chemical sciences ,biology.protein ,Macrolides ,Heterologous expression ,Bacillus subtilis - Abstract
The heterologous expression of the lobophorin biosynthetic gene cluster from marine-derived Streptomyces pactum SCSIO 02999 has led to the discovery of new analogues that carry d-kijanose (or its variants with a 3-amino or hydroxyl group) at C-9. The identification of intermediates resulting from the inactivation of lobG1 (encoding C-17 kijanosyltransferase) and lobG3 (encoding C-9 digitoxosyltransferase) demonstrates the substrate flexibility of LobG3 to also accept d-kijanose and its variants. Notably, two lobophorins with d-kijanose at C-9 show improved bioactivities.
- Published
- 2020
27. Heterologous expression of the trichostatin gene cluster and functional characterization ofN-methyltransferase TsnB8
- Author
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Wei Liu, Qingbo Zhang, Yiguang Zhu, Xiaodong Jiang, Changsheng Zhang, Vinay Gopal Jannu, Zhiwen Liu, Liang Ma, and Wenjun Zhang
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Methyltransferase ,Molecular Structure ,biology ,Chemistry ,organic chemicals ,Organic Chemistry ,Methyltransferases ,Hydroxamic Acids ,biology.organism_classification ,Biochemistry ,Streptomyces ,Molecular biology ,In vitro ,Trichostatin A ,Multigene Family ,Gene cluster ,medicine ,Histone deacetylase ,Heterologous expression ,Physical and Theoretical Chemistry ,Gene ,medicine.drug - Abstract
Trichostatins are potent inhibitors of histone deacetylase (HDAC). In this work, a new trichostatin derivative isotrichostatin RK (1) and five known compounds trichostatin RK (2), JBIR-111 (3), 9179B (4), trichostatic acid (5) and trichostatin A (6) were isolated from marine-derived Streptomyces sp. SCSIO 40028. The biosynthetic gene cluster (tsnB) for trichostatins was identified from Streptomyces sp. SCSIO 40028 and validated by heterologous expression in Streptomyces lividans TK64. N-Methyltransferase TsnB8 was demonstrated to catalyze successive methyltransfer reactions by in vivo gene inactivation and in vitro enzyme assays.
- Published
- 2020
28. Characterizing Two Cytochrome P450s in Tiacumicin Biosynthesis Reveals Reaction Timing for Tailoring Modifications
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Chengshan Yuan, Imran Khan, Yiguang Zhu, Haibo Zhang, Ziquan Yu, Qingbo Zhang, and Changsheng Zhang
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chemistry.chemical_classification ,Cytochrome ,biology ,Organic Chemistry ,Substrate (chemistry) ,Tiacumicin B ,Biochemistry ,Hydroxylation ,chemistry.chemical_compound ,Enzyme ,chemistry ,Biosynthesis ,Reaction timing ,biology.protein ,P450 Enzymes ,Physical and Theoretical Chemistry - Abstract
Functions of the tailoring enzymes for the biosynthesis of tiacumicin B (1) have been previously determined. However, the reaction timing remains elusive. Herein, we report the in vitro biochemical characterization of two P450 enzymes TiaP1 and TiaP2. The investigation of their substrate scope and kinetic parameters clearly demonstrates that the TiaP2-catalyzed C-20 hydroxylation is the first tailoring step and the TiaP1-catalyzed C-18 hydroxylation is the last step in the biosynthesis of 1.
- Published
- 2019
29. Host-dependent heterologous expression of berninamycin gene cluster leads to linear thiopeptide antibiotics
- Author
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Yiguang Zhu, Haibo Zhang, Zhiwen Liu, Qingbo Zhang, Bidhan Chandra De, Li-Ping Zhang, Bin Tan, Wenjun Zhang, Changsheng Zhang, and Guangtao Zhang
- Subjects
chemistry.chemical_classification ,biology ,Chemistry ,Organic Chemistry ,Streptomyces coelicolor ,biology.organism_classification ,Biochemistry ,Streptomyces ,Anti-Bacterial Agents ,Enzyme ,Gene cluster ,Heterologous expression ,Physical and Theoretical Chemistry ,Antibacterial activity ,Streptomyces albus ,Bacteria - Abstract
Berninamycins are a class of thiopeptide antibiotics with potent activity against Gram-positive bacteria. Heterologous expression of the berninamycin (ber) biosynthetic gene cluster from marine-derived Streptomyces sp. SCSIO 11878 in different terrestrial model Streptomyces hosts led to the production of berninamycins A (1) and B (2) in Streptomyces lividans SBT18 and Streptomyces coelicolor M1154, while two new linearized berninamycins J (3) and K (4) were obtained in Streptomyces albus J1074. Their structures were elucidated by detailed interpretation of NMR data and Marfey's method. Bioactivity assays showed that the linear thiopeptides 3 and 4 were less potent than 1 and 2 in antibacterial activity. This work indicates that undefined host-dependent enzymes might be responsible for generating the linear thiopeptides 3 and 4 in S. albus J1074.
- Published
- 2021
30. Functional characterization of the sulfotransferase TotS in totopotensamide biosynthesis
- Author
-
Bin Tan, Qingbo Zhang, Liping Zhang, Yiguang Zhu, and Changsheng Zhang
- Subjects
Organic Chemistry ,Drug Discovery ,Biochemistry - Published
- 2022
31. Discovery of an Unexpected 1,4-Oxazepine-Linked
- Author
-
Chunshuai, Huang, Chunfang, Yang, Wenjun, Zhang, Liping, Zhang, Yiguang, Zhu, and Changsheng, Zhang
- Subjects
Oxazepines ,Molecular Structure ,Cell Line, Tumor ,Polyketides ,Candida albicans ,Humans ,Gene Silencing ,Oxidoreductases ,Dimerization ,Micromonospora - Abstract
Fluostatins belong to the atypical angucyclinone aromatic polyketides featuring a distinctive tetracyclic benzo[
- Published
- 2021
32. Discovery of a new asymmetric dimer nenestatin B and implications of a dimerizing enzyme in a deep sea actinomycete
- Author
-
Chunfang Yang, Li-Ping Zhang, Qingbo Zhang, Wenjun Zhang, Changsheng Zhang, Xiaodong Jiang, Zhuangjie Fang, Haibo Zhang, Wei Liu, and Yiguang Zhu
- Subjects
Regulation of gene expression ,chemistry.chemical_classification ,biology ,Stereochemistry ,Dimer ,Organic Chemistry ,Mutant ,Bond formation ,biology.organism_classification ,Biochemistry ,Micromonospora echinospora ,chemistry.chemical_compound ,Monomer ,Enzyme ,chemistry ,Physical and Theoretical Chemistry ,Gene ,Dimerization - Abstract
Benzofluorene-containing atypical angucyclines are an important family of natural products with a broad spectrum of antibacterial and cytotoxic properties. Interestingly, symmetric and asymmetric dimers showed better activity than the monomer in this class of compounds. Herein, we reported the isolation of a new asymmetric dimer nenestatin B (2) from the deep sea actinomycete Micromonospora echinospora SCSIO 04089 and a monomer nenestatin C (3) from an NmrA family regulatory protein coding gene nes18 inactivated mutant. The structural elucidation of 3 indicated the essential role of Nes18 in the biosynthetic pathway of 2, specifically in dimerization via C–C bond formation.
- Published
- 2021
33. New piericidin derivatives from the marine-derived
- Author
-
Jing, Peng, Qingbo, Zhang, Xiaodong, Jiang, Liang, Ma, Ting, Long, Ziqian, Cheng, Changsheng, Zhang, and Yiguang, Zhu
- Subjects
Cell Line, Tumor ,Humans ,Antineoplastic Agents ,Streptomyces - Abstract
Two new piericidins A5 (
- Published
- 2021
34. Albumycin, a new isoindolequinone from Streptomyces albus J1074 harboring the fluostatin biosynthetic gene cluster
- Author
-
Wenjun Zhang, Changsheng Zhang, Chunfang Yang, Yiguang Zhu, Liang Ma, Zhuangjie Fang, and Chunshuai Huang
- Subjects
Methicillin-Resistant Staphylococcus aureus ,0301 basic medicine ,Magnetic Resonance Spectroscopy ,030106 microbiology ,Bacterial host ,Microbial Sensitivity Tests ,Isoindoles ,medicine.disease_cause ,01 natural sciences ,03 medical and health sciences ,Drug Discovery ,Gene cluster ,medicine ,Streptomyces albus ,Pharmacology ,Biological Products ,Molecular Structure ,biology ,010405 organic chemistry ,Chemistry ,Nuclear magnetic resonance spectroscopy ,biology.organism_classification ,Recombinant Proteins ,Streptomyces ,Anti-Bacterial Agents ,Biosynthetic Pathways ,0104 chemical sciences ,Biochemistry ,Staphylococcus aureus ,Heterologous expression ,Micromonospora rosaria ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
Heterologous expression of the fluostatin biosynthetic gene cluster from the marine-derived Micromonospora rosaria SCSIO N160 in Streptomyces albus J1074 led to the isolation of a novel isoindolequinone albumycin (1) and a known isoquinolinequinone mansouramycin A (2). The structure of 1 was elucidated on the basis of detailed 1D and 2D NMR spectroscopic analysis. Mansouramycin A (2) is active against methicillin-resistant Staphylococcus aureus ATCC 43300, with a MIC of 8 μg ml-1, while albumycin (1) displayed negligible antibacterial activities. This study represents another example of activation of secondary metabolites that are non-relevant to the heterologously introduced biosynthetic gene cluster in a bacterial host.
- Published
- 2019
35. Genome mining of cryptic tetronate natural products from a PKS-NRPS encoding gene cluster in
- Author
-
Yiguang, Zhu, Junfeng, Wang, Pengyun, Mou, Yan, Yan, Mengbin, Chen, and Yi, Tang
- Subjects
Fungal Proteins ,Biological Products ,4-Butyrolactone ,Multigene Family ,Hypocreales ,Genomics ,Peptide Synthases ,Polyketide Synthases ,Mass Spectrometry - Abstract
Trichoderma harzianum is a widely used biocontrol agent in agriculture. Obtaining a full inventory of the small molecules that can be biosynthesized from the encoded biosynthetic gene clusters (BGCs) is therefore useful for understanding associated plant-microbe and microbe-microbe interactions. Here we heterologously reconstituted a polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) encoding gene cluster from T. harzianum t-22 in Aspergillus nidulans A1145. Six new tetronate natural products trihazone A-F (1-6) were isolated and elucidated by HRESIMS and 1D and 2D NMR data. Three of the products contain an exocyclic olefin, which is derived from the oxidative decarboxylation of an α-ketoglutarate-dependent dioxygenase ThnC as shown by biochemical assays.
- Published
- 2021
36. A new xanthostatin analogue from the marine sponge-associated actinomycete
- Author
-
Siqiang, Chen, Qingbo, Zhang, Xinya, Zhang, Xiaodong, Jiang, Haibo, Zhang, Yiguang, Zhu, Changsheng, Zhang, and Liping, Zhang
- Subjects
Actinobacteria ,Molecular Structure ,Animals ,Streptomyces ,Anti-Bacterial Agents ,Porifera - Abstract
A new cyclo-heptadepsipeptide xanthostatin B (
- Published
- 2020
37. Natural products from mangrove sediments-derived microbes: Structural diversity, bioactivities, biosynthesis, and total synthesis
- Author
-
Kunlong Li, Siqiang Chen, Xiaoyan Pang, Jian Cai, Xinya Zhang, Yonghong Liu, Yiguang Zhu, and Xuefeng Zhou
- Subjects
Pharmacology ,Biological Products ,Organic Chemistry ,Drug Discovery ,Fungi ,General Medicine ,Ecosystem ,Streptomyces ,Anti-Bacterial Agents - Abstract
The mangrove forests are a complex ecosystem, and the microbial communities in mangrove sediments play a critical role in the biogeochemical cycles of mangrove ecosystems. Mangrove sediments-derived microbes (MSM), as a rich reservoir of natural product diversity, could be utilized in the exploration of new antibiotics or drugs. To understand the structural diversity and bioactivities of the metabolites of MSM, this review for the first time provides a comprehensive overview of 519 natural products isolated from MSM with their bioactivities, up to 2021. Most of the structural types of these compounds are alkaloids, lactones, xanthones, quinones, terpenoids, and steroids. Among them, 210 compounds are obtained from bacteria, most of which are from Streptomyces, while 309 compounds are from fungus, especially genus Aspergillus and Penicillium. The pharmacological mechanisms of some representative lead compounds are well studied, revealing that they have important medicinal potentials, such as piericidins with anti-renal cell cancer effects, azalomycins with anti-MRSA activities, and ophiobolins as antineoplastic agents. The biosynthetic pathways of representative natural products from MSM have also been summarized, especially ikarugamycin, piericidins, divergolides, and azalomycins. In addition, the total synthetic strategies of representative secondary metabolites from MSM are also reviewed, such as piericidin A and borrelidin. This review provides an important reference for the research status of natural products isolated from MSM and the lead compounds worthy of further development, and reveals that MSM have important medicinal values and are worthy of further development.
- Published
- 2022
38. Structural studies reveal flexible roof of active site responsible for ω-transaminase CrmG overcoming by-product inhibition
- Author
-
Yiguang Zhu, Weiming Zhu, Yan Dong, Kai Su, Xiaowen Tang, Changsheng Zhang, Zhijun Yu, Jinxin Xu, Ruibo Wu, Jinsong Liu, and Yulong Zhang
- Subjects
Stereochemistry ,Molecular Conformation ,Medicine (miscellaneous) ,Molecular Dynamics Simulation ,010402 general chemistry ,01 natural sciences ,Actinoalloteichus cyanogriseus ,General Biochemistry, Genetics and Molecular Biology ,Article ,Transaminase ,Substrate Specificity ,chemistry.chemical_compound ,Structure-Activity Relationship ,Biosynthesis ,Bacterial Proteins ,Catalytic Domain ,By-product ,Amino Acids ,Enzyme Inhibitors ,lcsh:QH301-705.5 ,Transaminases ,biology ,Molecular Structure ,010405 organic chemistry ,Rational design ,Active site ,0104 chemical sciences ,Actinobacteria ,Molecular Docking Simulation ,Structural biology ,chemistry ,lcsh:Biology (General) ,Biocatalysis ,biology.protein ,General Agricultural and Biological Sciences - Abstract
Amine compounds biosynthesis using ω-transaminases has received considerable attention in the pharmaceutical industry. However, the application of ω-transaminases was hampered by the fundamental challenge of severe by-product inhibition. Here, we report that ω-transaminase CrmG from Actinoalloteichus cyanogriseus WH1-2216-6 is insensitive to inhibition from by-product α-ketoglutarate or pyruvate. Combined with structural and QM/MM studies, we establish the detailed catalytic mechanism for CrmG. Our structural and biochemical studies reveal that the roof of the active site in PMP-bound CrmG is flexible, which will facilitate the PMP or by-product to dissociate from PMP-bound CrmG. Our results also show that amino acceptor caerulomycin M (CRM M), but not α-ketoglutarate or pyruvate, can form strong interactions with the roof of the active site in PMP-bound CrmG. Based on our results, we propose that the flexible roof of the active site in PMP-bound CrmG may facilitate CrmG to overcome inhibition from the by-product., Xu, Tang et al. show that ω-transaminase CrmG is insensitive to the inhibition from by-products α-ketoglutarate or pyruvate. They find that these by-products cannot interact strongly with the flexible roof of the active site in CrmG. This study provides insights into the rational design of transaminase to eliminate by-product inhibition.
- Published
- 2020
39. Proximicins F and G and Diproximicin A: Aminofurans from the Marine-Derived
- Author
-
Chunyan, Fang, Qingbo, Zhang, Yiguang, Zhu, Liping, Zhang, Wenjun, Zhang, Liang, Ma, Haibo, Zhang, and Changsheng, Zhang
- Subjects
Methicillin-Resistant Staphylococcus aureus ,Spectrometry, Mass, Electrospray Ionization ,Staphylococcus aureus ,Molecular Structure ,Micromonosporaceae ,Netropsin ,Microbial Sensitivity Tests ,Anti-Bacterial Agents ,Bacillus subtilis - Abstract
Overexpression of phosphopantetheinyl transferase (PPtase)-encoding genes
- Published
- 2020
40. Assembly Line and Post-PKS Modifications in the Biosynthesis of Marine Polyketide Natural Products
- Author
-
Chunfang Yang, Zhiwen Liu, Qingbo Zhang, Guangtao Zhang, Li-Ping Zhang, Liang Ma, Changsheng Zhang, Yiguang Zhu, and Lijuan Wang
- Subjects
chemistry.chemical_compound ,Polyketide ,Biosynthesis ,chemistry ,Structural diversity ,Computational biology ,Assembly line - Abstract
Marine polyketide natural products have attracted immense attentions due to their complex structures, significant bioactivities, and great potentials in drug leads discovery. It is well-known that fascinating assembly lines with unique enzymatic modifications, which could occur before, during and after polyketide chain assembly, contribute to the vast structural diversity of marine polyketides. This article describes the biosynthetic origin of more than 80 marine natural products derived from polyketide synthases (PKSs), with a focus on highlighting the current knowledge of chemistry and enzymology that are embedded in the assembly line and post-PKS modifications to support their structure diversity and important biological activities.
- Published
- 2020
41. Discovery and Biosynthesis of Neoenterocins Indicate a Skeleton Rearrangement of Enterocin
- Author
-
Xiaodong Jiang, Yiguang Zhu, Jinsong Liu, Haibo Zhang, Liujuan Zheng, Changsheng Zhang, Kumar Saurav, Wenjun Zhang, and Qingbo Zhang
- Subjects
Bridged-Ring Compounds ,biology ,010405 organic chemistry ,Stereochemistry ,Organic Chemistry ,food and beverages ,010402 general chemistry ,biology.organism_classification ,01 natural sciences ,Biochemistry ,Streptomyces ,0104 chemical sciences ,chemistry.chemical_compound ,Biosynthesis ,chemistry ,Cell Line, Tumor ,Polyketides ,Gene cluster ,Humans ,Heterologous expression ,Physical and Theoretical Chemistry ,Gene ,Cell Proliferation - Abstract
Two polyketides neoenterocins A (1) and B (2), featuring a neighboring dicarbonyl motif and a furan-containing 5/6 ring system, were isolated from the enterocin producer Streptomyces sp. SCSIO 11863. Heterologous expression, gene disruptions, and isotope feeding experiments indicated that 1 and 2 were derived from the enterocin biosynthetic gene cluster. However, 2 was demonstrated as an artifact from enterocin via a unique skeleton rearrangement.
- Published
- 2019
42. Endophyte Bacillus subtilis evade plant defense by producing lantibiotic subtilomycin to mask self-produced flagellin
- Author
-
Yuanyuan Xu, Chen H, Ming Sun, Jianyi Xu, Congzhi Li, Donghai Peng, Lifang Ruan, Jinshui Zheng, Yun Deng, Qing-Dong Qi, and Yiguang Zhu
- Subjects
0303 health sciences ,fungi ,food and beverages ,Medicine (miscellaneous) ,Bacillus subtilis ,Biology ,Commensalism ,biology.organism_classification ,Endophyte ,General Biochemistry, Genetics and Molecular Biology ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,lcsh:Biology (General) ,Symbiosis ,Plant defense against herbivory ,biology.protein ,Colonization ,General Agricultural and Biological Sciences ,lcsh:QH301-705.5 ,030217 neurology & neurosurgery ,Bacteria ,Flagellin ,030304 developmental biology - Abstract
Microbes can enter into healthy plants as endophytes and confer beneficial functions. The entry of commensal microbes into plants involves penetrating plant defense. Most mechanisms about overcoming plant defense are focused on adapted pathogens, while the mechanism involved in beneficial endophyte evades plant defense to achieve harmonious commensalism is unclear. Here, we discover a mechanism that an endophyte bacterium Bacillus subtilis BSn5 reduce to stimulate the plant defensive response by producing lantibiotic subtilomycin to bind self-produced flagellin. Subtilomycin bind with flagellin and affect flg22-induced plant defense, by which means promotes the endophytic colonization in A. thaliana. Subtilomycin also promotes the BSn5 colonization in a distinct plant, Amorphophallus konjac, where the BSn5 was isolated. Our investigation shows more independent subtilomycin/-like producers are isolated from distinct plants. Our work unveils a common strategy that is used for bacterial endophytic colonization.
- Published
- 2019
43. Diisonitrile Natural Product SF2768 Functions As a Chalkophore That Mediates Copper Acquisition in Streptomyces thioluteus
- Author
-
Xueshi Huang, Panlei Yang, Xu Zhang, Lijuan Wang, Mengyi Zhu, Yiguang Zhu, Li Han, Shengqing Li, Qingbo Zhang, Zihui Liu, Jing He, and Yun Deng
- Subjects
0301 basic medicine ,Siderophore ,Stereochemistry ,Electrospray ionization ,Mutant ,Siderophores ,01 natural sciences ,Biochemistry ,Streptomyces ,Streptomyces thioluteus ,03 medical and health sciences ,chemistry.chemical_compound ,Biosynthesis ,Nonribosomal peptide ,Nitriles ,Gene cluster ,Peptide Synthases ,Chelating Agents ,chemistry.chemical_classification ,Biological Products ,biology ,010405 organic chemistry ,Amino Sugars ,Biological Transport ,Gene Expression Regulation, Bacterial ,General Medicine ,biology.organism_classification ,Anti-Bacterial Agents ,0104 chemical sciences ,030104 developmental biology ,chemistry ,Multigene Family ,Molecular Medicine ,Copper - Abstract
A nonribosomal peptide synthetase (NRPS) gene cluster (sfa) was identified in Streptomyces thioluteus to direct the biosynthesis of the diisonitrile antibiotic SF2768. Its biosynthetic pathway was reasonably proposed based on bioinformatics analysis, metabolic profiles of mutants, and the elucidation of the intermediate and shunt product structures. Bioinformatics-based alignment found a putative ATP-binding cassette (ABC) transporter related to iron import within the biosynthetic gene cluster, which implied that the product might be a siderophore. However, characterization of the metal-binding properties by high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), metal-ligand titration, thin-layer chromatography (TLC), and chrome azurol S (CAS) assays revealed that the final product SF2768 and its diisonitrile derivatives specifically bind copper, rather than iron, to form stable complexes. Inductively coupled plasma mass spectrometry (ICP-MS) analysis revealed that the intracellular cupric content of S. thioluteus significantly increased upon incubation with the copper-SF2768 complex, direct evidence for the copper acquisition function of SF2768. Further in vivo functional characterization of the transport elements for the copper-SF2768 complexes not only confirmed the chalkophore identity of the compound but also gave initial clues into the copper uptake mechanism of this nonmethanotrophic microorganism.
- Published
- 2017
44. Genome Mining and Activation of a Silent PKS/NRPS Gene Cluster Direct the Production of Totopotensamides
- Author
-
Changsheng Zhang, Chen Ruidong, Liujuan Zheng, Yiguang Zhu, Bin Tan, Qingbo Zhang, and Huixian Li
- Subjects
0301 basic medicine ,Streptomyces pactum ,Biochemistry ,Streptomyces ,03 medical and health sciences ,Polyketide ,chemistry.chemical_compound ,Nonribosomal peptide ,Glycosyltransferase ,Gene cluster ,Glycosyl ,Peptide Synthases ,Physical and Theoretical Chemistry ,Regulator gene ,chemistry.chemical_classification ,Molecular Structure ,biology ,Organic Chemistry ,biology.organism_classification ,030104 developmental biology ,chemistry ,Multigene Family ,biology.protein ,Polyketide Synthases ,Genome, Bacterial - Abstract
A 92 kb silent hybrid polyketide and nonribosomal peptide gene cluster in marine-derived Streptomyces pactum SCSIO 02999 was activated by genetically manipulating the regulatory genes, including the knockout of two negative regulators (totR5 and totR3) and overexpression of a positive regulator totR1, to direct the production of the known totopotensamides (TPMs) A (1) and B (3) and a novel sulfonate-containing analogue TPM C (2). Inactivation of totG led to accumulation of TPM B (3) lacking the glycosyl moiety, which indicated TotG as a dedicated glycosyltransferase in the biosynthesis of 1 and 2.
- Published
- 2017
45. Collaborative sparse representation leaning model for RGBD action recognition
- Author
-
S.H. Li, Zhiqiang Gao, C. Wang, Hua Zhang, and Yiguang Zhu
- Subjects
Modalities ,Boosting (machine learning) ,Computer science ,business.industry ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,020207 software engineering ,Pattern recognition ,Classification scheme ,02 engineering and technology ,Sparse approximation ,Reconstruction error ,Signal Processing ,0202 electrical engineering, electronic engineering, information engineering ,Media Technology ,Action recognition ,RGB color model ,020201 artificial intelligence & image processing ,Computer vision ,Computer Vision and Pattern Recognition ,Artificial intelligence ,Electrical and Electronic Engineering ,business ,Temporal modeling - Abstract
We formulate the fusion of RGB and depth modalities as a collaborative sparse representation leaning problem.RGB and depth features are joint reconstructed, and their respective advantages are utilized to significantly boost the recognition efficiency.A collaborative sparse representation leaning model is specially designed for RGBD action recognition, which automatic make fusion to find the optimal reconstruction coefficients, further boosting the performance. Multi-modalities action recognition becomes a hot research topic, and this paper proposes a collaborative sparse representation leaning model for RGB-D action recognition where RGB and depth information are adaptive fused. Specifically, dense trajectory feature is firstly extracted and Bag-of-Word (BoW) weight scheme is employed for RGB modality, and then for depth modality, the human pose representation model (HPM) and temporal modeling (TM) representation are utilized. Meanwhile, the collaborative reconstruction structure and corresponding objective functions for the multiple modalities are designed, and then the proposed model is collaboratively optimized which is used to discover the latent complementary information between RGB and depth data. Finally, the collaborative reconstruction error is employed as our classification scheme. Large scale experimental results on challenging and public DHA, M2I and Northwestern-UCLA action datasets show that the performances of our model on two modalities are much better than traditional sole modality, which can boost the performance of human action recognition by taking advance of complementary characteristics from both RGB and depth modalities.
- Published
- 2017
46. Antibacterial phenylspirodrimanes from the marine-derived fungus Stachybotrys sp. SCSIO 40434
- Author
-
Zhong-Bo Zhou, Li-Ping Zhang, Xiaodong Jiang, Changsheng Zhang, Yiguang Zhu, Jing Peng, Qingbo Zhang, and Pengyun Mou
- Subjects
Methicillin-Resistant Staphylococcus aureus ,Aquatic Organisms ,China ,Staphylococcus aureus ,Fungus ,medicine.disease_cause ,01 natural sciences ,Microbiology ,Stachybotrys sp ,Stachybotrys ,Drug Discovery ,medicine ,Pharmacology ,Biological Products ,Pacific Ocean ,Molecular Structure ,biology ,010405 organic chemistry ,Chemistry ,Absolute configuration ,General Medicine ,biology.organism_classification ,Methicillin-resistant Staphylococcus aureus ,Anti-Bacterial Agents ,0104 chemical sciences ,Micrococcus luteus ,010404 medicinal & biomolecular chemistry ,Antibacterial activity - Abstract
Five new phenylspirodrimanes, stachybomycins A − E (1–5), together with four known compounds (6–9), were isolated from the marine-derived fungus Stachybotrys sp. SCSIO 40434. Their structures were elucidated by comprehensive spectroscopic analyses of NMR and HRESIMS. The absolute configuration of 1 was confirmed by single crystal X-ray diffraction analysis. Compounds 5 and 7 showed moderate antibacterial activities against Micrococcus luteus, Staphylococcus aureus and methicillin resistant Staphylococcus aureus with minimal inhibition concentration (MIC) values of 8, 16 and 16 μg mL−1, respectively.
- Published
- 2021
47. Pyrazolofluostatins A–C, Pyrazole-Fused Benzo[a]fluorenes from South China Sea-Derived Micromonospora rosaria SCSIO N160
- Author
-
Haibo Zhang, Li-Ping Zhang, Changsheng Zhang, Chunshuai Huang, Yiguang Zhu, Chengshan Yuan, Chunfang Yang, Wenjun Zhang, and Qingbo Zhang
- Subjects
China ,Fluorenes ,South china ,Molecular Structure ,010405 organic chemistry ,Stereochemistry ,Organic Chemistry ,Carbon skeleton ,Pyrazole ,010402 general chemistry ,Ring (chemistry) ,Micromonospora ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Pyrazoles ,Physical and Theoretical Chemistry ,Micromonospora rosaria - Abstract
Pyrazolofluostatins A–C (1–3), three new benzo[a]fluorenes with an unprecedented carbon skeleton, were obtained from the South China Sea-derived Micromonospora rosaria SCSIO N160. Their structures were elucidated by extensive spectroscopic analyses. The structure of pyrazolofluostatin A (1) was confirmed by X-ray crystallographic analysis. Notably, 1–3 possessed a benzo[cd]indeno[2,1-f]indazol skeleton with a pyrazole-fused 6/5/6/6/5 pentacyclic ring system. Pyrazolofluostatin A (1) showed moderate antioxidation activity (EC50 48.6 μM).
- Published
- 2017
48. Characterization of the flavoenzyme XiaK as an N-hydroxylase and implications in indolosesquiterpene diversification
- Author
-
Ang Li, Huixian Li, Yu Sun, Shu-Ming Li, Qingbo Zhang, Hanning Zhu, Changlin Tian, Hung-wen Liu, Changsheng Zhang, Yiguang Zhu, Li-Ping Zhang, Lu Yu, and Yuemao Shen
- Subjects
010405 organic chemistry ,Stereochemistry ,Carbazole ,General Chemistry ,010402 general chemistry ,01 natural sciences ,In vitro ,0104 chemical sciences ,Catalysis ,Adduct ,Hydroxylation ,chemistry.chemical_compound ,chemistry ,Biosynthesis ,Biotransformation ,In vivo - Abstract
Flavoenzymes are ubiquitous in biological systems and catalyze a diverse range of chemical transformations. The flavoenzyme XiaK from the biosynthetic pathway of the indolosesquiterpene xiamycin A is demonstrated to mediate the in vivo biotransformation of xiamycin A into multiple products, including a chlorinated adduct as well as dimers characterized by C–N and N–N linkages that are hypothesized to form via radical-based mechanisms. Isolation and characterization of XiaK in vitro shows that it acts as a flavin-dependent N-hydroxylase that catalyzes the hydroxylation of xiamycin A at the carbazole nitrogen to form N-hydroxyxiamycin, a product which was overlooked in earlier in vivo experiments because its chemical and chromatographic properties are similar to those of oxiamycin. N-Hydroxyxiamycin is shown to be unstable under aerobic conditions, and characterization by electron paramagnetic resonance spectroscopy demonstrates formation of an N-hydroxycarbazole radical adduct. This radical species is proposed to serve as a key intermediate leading to the formation of the multiple xiamycin A adducts. This study suggests that non-enzyme catalyzed reactions may play a greater role in the biosynthesis of natural products than has been previously recognized.
- Published
- 2017
49. Activation and characterization of a cryptic gene cluster reveals a cyclization cascade for polycyclic tetramate macrolactams
- Author
-
Subhasish Saha, Qingbo Zhang, Yuchan Chen, Liping Zhang, Wei Liu, Haibo Zhang, Weimin Zhang, Chengshan Yuan, Wenjun Zhang, Guangtao Zhang, Changsheng Zhang, and Yiguang Zhu
- Subjects
Genetics ,chemistry.chemical_classification ,biology ,010405 organic chemistry ,Stereochemistry ,Chemistry ,Streptomyces pactum ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Cyclase ,0104 chemical sciences ,Oxidoreductase ,Polyketide synthase ,Gene cluster ,biology.protein ,Heterologous expression ,Gene ,Alcohol dehydrogenase - Abstract
Polycyclic tetramate macrolactams (PTMs) are a growing class of natural products and are derived from a hybrid polyketide synthase (PKS)/non-ribosomal peptide synthetase (NRPS) pathway. PTM biosynthetic gene clusters are conserved and widely distributed in bacteria, however, most of them remain silent. Herein we report the activation of a PTM gene cluster in marine-derived Streptomyces pactum SCSIO 02999 by promoter engineering and heterologous expression, leading to the discovery of six new PTMs, pactamides A-F (11-16), with potent cytotoxic activity upon several human cancer cell lines. In vivo gene disruption experiments and in vitro biochemical assays reveal a reductive cyclization cascade for polycycle formation, with reactions sequentially generating the 5, 5/5 and 5/5/6 carbocyclic ring systems, catalysed by the phytoene dehydrogenase PtmB2, the oxidoreductase PtmB1, and the alcohol dehydrogenase PtmC, respectively. Furthermore, PtmC was demonstrated as a bifunctional cyclase for catalyzing the formation of the inner five-membered ring in ikarugamycin. This study suggests the possibility of finding more bioactive PTMs by genome mining and discloses a general mechanism for the formation of 5/5/6-type carbocyclic rings in PTMs.
- Published
- 2017
50. A new uridine derivative and a new indole derivative from the coral-associated actinomycete
- Author
-
Zhuangjie, Fang, Siqiang, Chen, Yiguang, Zhu, Jie, Li, Imran, Khan, Qingbo, Zhang, and Changsheng, Zhang
- Subjects
Indoles ,Molecular Structure ,Cell Line, Tumor ,Fermentation ,Pseudonocardia ,Drug Evaluation, Preclinical ,Animals ,Humans ,Antineoplastic Agents ,Microbial Sensitivity Tests ,Anthozoa ,Uridine ,Anti-Bacterial Agents - Abstract
A new uridine derivative 11457 A (
- Published
- 2019
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