共查询到20条相似文献,搜索用时 15 毫秒
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Dr. Hayama Tsutsumi Prof. Yohei Katsuyama Dr. Takeaki Tezuka Dr. Rei Miyano Dr. Yuki Inahashi Dr. Yoko Takahashi Dr. Takuji Nakashima Prof. Yasuo Ohnishi 《Chembiochem : a European journal of chemical biology》2022,23(3):e202100517
Indolizidine alkaloids, which have versatile bioactivities, are produced by various organisms. Although the biosynthesis of some indolizidine alkaloids has been studied, the enzymatic machinery for their biosynthesis in Streptomyces remains elusive. Here, we report the identification and analysis of the biosynthetic gene cluster for iminimycin, an indolizidine alkaloid with a 6-5-3 tricyclic system containing an iminium cation from Streptomyces griseus. The gene cluster has 22 genes, including four genes encoding polyketide synthases (PKSs), which consist of eight modules in total. In vitro analysis of the first module revealed that its acyltransferase domain selects malonyl-CoA, although predicted to select methylmalonyl-CoA. Inactivation of seven tailoring enzyme-encoding genes and structural elucidation of four compounds accumulated in mutants provided important insights into iminimycin biosynthesis, although some of these compounds appeared to be shunt products. This study expands our knowledge of the biosynthetic machinery of indolizidine alkaloids and the enzymatic chemistry of PKS. 相似文献
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Piotr Siupka Frederik Teilfeldt Hansen Aleksandra Schier Simone Rocco Trine Srensen Zofia Piotrowska-Seget 《International journal of molecular sciences》2021,22(14)
Crop infections by fungi lead to severe losses in food production and pose risks for human health. The increasing resistance of pathogens to fungicides has led to the higher usage of these chemicals, which burdens the environment and highlights the need to find novel natural biocontrol agents. Members of the genus Streptomyces are known to produce a plethora of bioactive compounds. Recently, researchers have turned to extreme and previously unexplored niches in the search for new strains with antimicrobial activities. One such niche are underground coal mine environments. We isolated the new Streptomyces sp. MW-W600-10 strain from coal mine water samples collected at 665 m below ground level. We examined the antifungal activity of the strain against plant pathogens Fusarium culmorum DSM62188 and Nigrospora oryzae roseF7. Furthermore, we analyzed the strain’s biosynthetic potential with the antiSMASH tool. The strain showed inhibitory activity against both fungi strains. Genome mining revealed that it has 39 BGCs, among which 13 did not show similarity to those in databases. Additionally, we examined the activity of the Streptomyces sp. S-2 strain isolated from black soot against F. culmorum DSM62188. These results show that coal-related strains could be a source of novel bioactive compounds. Future studies will elucidate their full biotechnological potential. 相似文献
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Identification and Characterization of a Welwitindolinone Alkaloid Biosynthetic Gene Cluster in the Stigonematalean Cyanobacterium Hapalosiphon welwitschii 下载免费PDF全文
Dr. Matthew L. Hillwig Heather A. Fuhrman Kuljira Ittiamornkul Tyler J. Sevco Daniel H. Kwak Prof. Dr. Xinyu Liu 《Chembiochem : a European journal of chemical biology》2014,15(5):665-669
The identification of a 36 kb welwitindolinone (wel) biosynthetic gene cluster in Hapalosiphon welwitschii UTEX B1830 is reported. Characterization of the enzymes responsible for assembling the early biosynthetic intermediates geranyl pyrophosphate and 3‐((Z)‐2′‐isocyanoethenyl)indole as well as a dedicated N‐methyltransferase in the maturation of N‐methylwelwitindolinone C isothiocyanate solidified the link between the wel pathway and welwitindolinone biosynthesis. Comparative analysis of the ambiguine and welwitindolinone biosynthetic pathways in two different organisms provided insights into the origins of diverse structures within hapalindole‐type molecules. 相似文献
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Identification and Characterization of the Streptazone E Biosynthetic Gene Cluster in Streptomyces sp. MSC090213JE08 下载免费PDF全文
Shoto Ohno Dr. Yohei Katsuyama Yuka Tajima Dr. Miho Izumikawa Dr. Motoki Takagi Dr. Manabu Fujie Dr. Noriyuki Satoh Dr. Kazuo Shin‐ya Dr. Yasuo Ohnishi 《Chembiochem : a European journal of chemical biology》2015,16(16):2385-2391
Streptazone derivatives isolated from Streptomyces species are piperidine alkaloids with a cyclopenta[b]pyridine scaffold. Previous studies indicated that these compounds are polyketides, but the biosynthetic enzymes responsible for their synthesis are unknown. Here, we have identified the streptazone E biosynthetic gene cluster in Streptomyces sp. MSC090213JE08, which encodes a modular type I PKS and tailoring enzymes that include an aminotransferase, three oxidoreductases, and two putative cyclases. The functions of the six tailoring enzymes were analyzed by gene disruption, and two putative biosynthetic intermediates that accumulated in particular mutants were structurally elucidated. On the basis of these results, we propose a pathway for the biosynthesis of streptazone E in which the two putative cyclases of the nuclear transport factor 2–like superfamily are responsible for C?C bond formation coupled with epoxide ring opening to give the five‐membered ring of streptazone E. 相似文献
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Yuhai Jiang Dr. Haoxin Wang Dr. Chunhua Lu Yanjiao Ding Dr. Yaoyao Li Prof. Dr. Yuemao Shen 《Chembiochem : a European journal of chemical biology》2013,14(12):1468-1475
Genome sequence analysis of Streptomyces sp. LZ35 has revealed a large number of secondary metabolite pathways, including one encoded in an orphan type I polyketide synthase gene cluster that contains a putative chorismatase/3‐hydroxybenzoate synthase gene. Mutagenesis and comparative metabolic profiling led to the identification of cuevaene A as the metabolic product of the gene cluster, thus making it the first 3‐HBA containing polyketide biosynthetic gene cluster described to date. Cuv10 was proven to be responsible for the conversion of chorismate into 3‐HBA; Cuv18 is speculated to be responsible for the 6‐hydroxylation of 3‐HBA during polyketide chain elongation. Additionally, several pathway‐specific regulatory factors that affect the production of cuevaene A were identified. Our results indicate that targeted inactivation of a gene followed by comparative metabolic profiling is a useful approach to identify and characterize cryptic biosynthetic gene clusters. 相似文献
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Dr. Marta Wojnowska Dr. Xuan Feng Yawen Chen Dr. Hai Deng Prof. Dr. David O'Hagan 《Chembiochem : a European journal of chemical biology》2023,24(5):e202200684
The gene cluster in Streptomyces calvus associated with the biosynthesis of the fluoro- and sulfamyl-metabolite nucleocidin was interrogated by systematic gene knockouts. Out of the 26 gene deletions, most did not affect fluorometabolite production, nine abolished sulfamylation but not fluorination, and three precluded fluorination, but had no effect on sulfamylation. In addition to nucI, nucG, nucJ, nucK, nucL, nucN, nucO, nucQ and nucP, we identified two genes (nucW, nucA), belonging to a phosphoadenosine phosphosulfate (PAPS) gene cluster, as required for sulfamyl assembly. Three genes (orf(−3), orf2 and orf3) were found to be essential for fluorination, although the activities of their protein products are unknown. These genes as well as nucK, nucN, nucO and nucPNP, whose knockouts produced results differing from those described in a recent report, were also deleted in Streptomyces virens – with confirmatory outcomes. This genetic profile should inform biochemistry aimed at uncovering the enzymology behind nucleocidin biosynthesis. 相似文献
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Inside Cover: Identification and Characterization of a Welwitindolinone Alkaloid Biosynthetic Gene Cluster in the Stigonematalean Cyanobacterium Hapalosiphon welwitschii (ChemBioChem 5/2014) 下载免费PDF全文
Dr. Matthew L. Hillwig Heather A. Fuhrman Kuljira Ittiamornkul Tyler J. Sevco Daniel H. Kwak Prof. Dr. Xinyu Liu 《Chembiochem : a European journal of chemical biology》2014,15(5):626-626
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Identification and Characterization of the Carbapenem MM 4550 and its Gene Cluster in Streptomyces argenteolus ATCC 11009 下载免费PDF全文
Dr. Rongfeng Li Evan P. Lloyd Dr. Kristos A. Moshos Prof. Craig A. Townsend 《Chembiochem : a European journal of chemical biology》2014,15(2):320-331
Nearly 50 naturally occurring carbapenem β‐lactam antibiotics, most produced by Streptomyces, have been identified. The structural diversity of these compounds is limited to variance of the C‐2 and C‐6 side chains as well as the stereochemistry at C‐5/C‐6. These structural motifs are of interest both for their antibiotic effects and their biosynthesis. Although the thienamycin gene cluster is the only active gene cluster publically available in this group, more comparative information is needed to understand the genetic basis of these structural differences. We report here the identification of MM 4550, a member of the olivanic acids, as the major carbapenem produced by Streptomyces argenteolus ATCC 11009. Its gene cluster was also identified by degenerate PCR and targeted gene inactivation. Sequence analysis revealed that the genes encoding the biosynthesis of the bicyclic core and the C‐6 and C‐2 side chains are well conserved in the MM 4550 and thienamycin gene clusters. Three new genes, cmmSu, cmm17 and cmmPah were found in the new cluster, and their putative functions in the sulfonation and epimerization of MM 4550 are proposed. Gene inactivation showed that, in addition to cmmI, two new genes, cmm22 and ‐23, encode a two‐component response system thought to regulate the production of MM 4550. Overexpression of cmmI, cmm22 and cmm23 promoted MM 4550 production in an engineered strain. Finally, the involvement and putative roles of all genes in the MM 4550 cluster are proposed based on the results of bioinformatics analysis, gene inactivation, and analysis of disruption mutants. Overall, the differences between the thienamycin and MM 4550 gene clusters are reflected in characteristic structural elements and provide new insights into the biosynthesis of the complex carbapenems. 相似文献
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Jacob C. Carlson J. L. Fortman Dr. Yojiro Anzai Dr. Shengying Li Douglas A. Burr Dr. David H. Sherman Prof. 《Chembiochem : a European journal of chemical biology》2010,11(4):564-572
The structurally intriguing bicyclic ketal moiety of tirandamycin is common to several acyl‐tetramic acid antibiotics, and is a key determinant of biological activity. We have identified the tirandamycin biosynthetic gene cluster from the environmental marine isolate Streptomyces sp. 307–9, thus providing the first genetic insight into the biosynthesis of this natural product scaffold. Sequence analysis revealed a hybrid polyketide synthase–nonribosomal peptide synthetase gene cluster with a colinear domain organization, which is entirely consistent with the core structure of the tirandamycins. We also identified genes within the cluster that encode candidate tailoring enzymes for elaboration and modification of the bicyclic ketal system. Disruption of tamI, which encodes a presumed cytochrome P450, led to a mutant strain deficient in production of late stage tirandamycins that instead accumulated tirandamycin C, an intermediate devoid of any post assembly‐line oxidative modifications. 相似文献
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Genome Mining‐Directed Activation of a Silent Angucycline Biosynthetic Gene Cluster in Streptomyces chattanoogensis 下载免费PDF全文
Dr. Zhenxing Zhou Qingqing Xu Dr. Qingting Bu Dr. Yuanyang Guo Dr. Shuiping Liu Yu Liu Dr. Yiling Du Prof. Yongquan Li 《Chembiochem : a European journal of chemical biology》2015,16(3):496-502
Genomic sequencing of actinomycetes has revealed the presence of numerous gene clusters seemingly capable of natural product biosynthesis, yet most clusters are cryptic under laboratory conditions. Bioinformatics analysis of the completely sequenced genome of Streptomyces chattanoogensis L10 (CGMCC 2644) revealed a silent angucycline biosynthetic gene cluster. The overexpression of a pathway‐specific activator gene under the constitutive ermE* promoter successfully triggered the expression of the angucycline biosynthetic genes. Two novel members of the angucycline antibiotic family, chattamycins A and B, were further isolated and elucidated. Biological activity assays demonstrated that chattamycin B possesses good antitumor activities against human cancer cell lines and moderate antibacterial activities. The results presented here provide a feasible method to activate silent angucycline biosynthetic gene clusters to discover potential new drug leads. 相似文献
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Chaoxuan Li Dr. Kathryn E. Roege Wendy L. Kelly Prof. 《Chembiochem : a European journal of chemical biology》2009,10(6):1064-1072
More than meets the I : The biosynthetic gene cluster for indanomycin was identified from Streptomyces antibioticus NRRL 8167. The framework of the indanomycins includes a tetrahydropyran and a central indane ring system. The final module of the indanomycin polyketide synthase possesses an unusual terminal module lacking an integrated thioesterase.
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Production of a Novel Amide‐Containing Polyene by Activating a Cryptic Biosynthetic Gene Cluster in Streptomyces sp. MSC090213JE08 下载免费PDF全文
Danyao Du Dr. Yohei Katsuyama Dr. Hiroyasu Onaka Manabu Fujie Dr. Noriyuki Satoh Dr. Kazuo Shin‐ya Dr. Yasuo Ohnishi 《Chembiochem : a European journal of chemical biology》2016,17(15):1464-1471
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Fumitaka Kudo Dr. Atsushi Motegi Kazutoshi Mizoue Dr. Tadashi Eguchi Prof. Dr. 《Chembiochem : a European journal of chemical biology》2010,11(11):1574-1582
FD‐891 is a 16‐membered cytotoxic antibiotic macrolide that is especially active against human leukemia such as HL‐60 and Jurkat cells. We identified the FD‐891 biosynthetic (gfs) gene cluster from the producer Streptomyces graminofaciens A‐8890 by using typical modular type I polyketide synthase (PKS) genes as probes. The gfs gene cluster contained five typical modular type I PKS genes (gfsA, B, C, D, and E), a cytochrome P450 gene (gfsF), a methyltransferase gene (gfsG), and a regulator gene (gfsR). The gene organization of PKSs agreed well with the basic polyketide skeleton of FD‐891 including the oxidation states and α‐alkyl substituent determined by the substrate specificities of the acyltransferase (AT) domains. To clarify the involvement of the gfs genes in the FD‐891 biosynthesis, the P450 gfsF gene was inactivated; this resulted in the loss of FD‐891 production. Instead, the gfsF gene‐disrupted mutant accumulated a novel FD‐891 analogue 25‐O‐methyl‐FD‐892, which lacked the epoxide and the hydroxyl group of FD‐891. Furthermore, the recombinant GfsF enzyme coexpressed with putidaredoxin and putidaredoxin reductase converted 25‐O‐methyl‐FD‐892 into FD‐891. In the course of the GfsF reaction, 10‐deoxy‐FD‐891 was isolated as an enzymatic reaction intermediate, which was also converted into FD‐891 by GfsF. Therefore, it was clearly found that the cytochrome P450 GfsF catalyzes epoxidation and hydroxylation in a stepwise manner in the FD‐891 biosynthesis. These results clearly confirmed that the identified gfs genes are responsible for the biosynthesis of FD‐891 in S. graminofaciens. 相似文献
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