keyword
https://read.qxmd.com/read/32486092/bioactive-potential-of-extracts-of-labrenzia-aggregata-strain-usba-371-a-halophilic-bacterium-isolated-from-a-terrestrial-source
#21
JOURNAL ARTICLE
Carolina Díaz-Cárdenas, Laura Yinneth Rojas, Susana Fiorentino, Monica P Cala, Jorge I Díaz, Freddy A Ramos, Jean Armengaud, Silvia Restrepo, Sandra Baena
Previous studies revealed the potential of Labrenzia aggregata USBA 371 to produce cytotoxic metabolites. This study explores its metabolic diversity and compounds involved in its cytotoxic activity. Extracts from the extracellular fraction of strain USBA 371 showed high levels of cytotoxic activity associated with the production of diketopiperazines (DKPs). We purified two compounds and a mixture of two other compounds from this fraction. Their structures were characterized by 1D and 2D nuclear magnetic resonance (NMR)...
May 29, 2020: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/32111589/multistep-metabolic-engineering-of-bacillus-licheniformis-to-improve-pulcherriminic-acid-production
#22
JOURNAL ARTICLE
Shiyi Wang, Huan Wang, Dan Zhang, Xiaoyun Li, Jiang Zhu, Yangyang Zhan, Dongbo Cai, Qin Wang, Xin Ma, Dong Wang, Shouwen Chen
The cyclodipeptide pulcherriminic acid produced by Bacillus licheniformis is derived from cyclo(L-Leu-L-Leu) and possesses excellent antibacterial activities. In this study, we achieved high-level production of pulcherriminic acid via multistep metabolic engineering of B. licheniformis DWc9n*. Firstly, we increased leucine (Leu) supply by overexpressing the ilvBHC-leuABCD operon and ilvD involved in Leu biosynthesis to obtain strain W1, and the engineered strain W2 was further attained by deletion of gene bkdAB encoding branched-chain α-keto acid dehydrogenase in W1...
February 28, 2020: Applied and Environmental Microbiology
https://read.qxmd.com/read/31589428/diketopiperazines-synthesis-gene-in-shewanella-baltica-and-roles-of-diketopiperazines-and-resveratrol-in-quorum-sensing
#23
JOURNAL ARTICLE
Junli Zhu, Yuwei Zhang, Jingmin Deng, Hanyun Jiang, Liumin Zhuang, Wei Ye, Jiayu Ma, Jingyang Jiang, Lifang Feng
The synthesis pathways of quorum sensing (QS) signal molecules and the mechanism of action of quorum sensing inhibitors (QSIs) have gained considerable attention as research topics in the field of food preservation. Here, Shewanella baltica was detected as the specific spoilage organism in large yellow croaker during 4 °C storage, and it produced the QS signal molecules autoinducer-2 (AI-2) and diketopiperazines (DKPs). Then, a cyclodipeptide synthase (CDPS) homologous gene, sb1370, was screened, and knockout and rescue results revealed that this gene was involved in DKP synthesis but not in AI-2 synthesis, and it also played an important role in QS...
October 7, 2019: Journal of Agricultural and Food Chemistry
https://read.qxmd.com/read/31407584/genome-mining-and-enzymatic-total-biosynthesis-of-purincyclamide
#24
JOURNAL ARTICLE
Jing Shi, Xiang Xu, Er Juan Zhao, Bo Zhang, Wei Li, Yang Zhao, Rui Hua Jiao, Ren Xiang Tan, Hui Ming Ge
A cyclodipeptide synthase-containing gene cluster ( pcm ) was identified in Streptomyces chrestomyceticus NA4264 through genome mining. Heterologous expression of the cryptic pcm gene cluster in Streptomyces albus led to the production of a new highly modified cyclodipeptide named purincyclamide ( 1 ). Bioinformatic analysis and gene knockout experiments revealed the biosynthetic pathway. The production of 1 was achieved through a one-pot enzymatic reaction.
August 13, 2019: Organic Letters
https://read.qxmd.com/read/31239480/reprogramming-escherichia-coli-for-the-production-of-prenylated-indole-diketopiperazine-alkaloids
#25
JOURNAL ARTICLE
Pavlina Dubois, Isabelle Correia, Fabien Le Chevalier, Steven Dubois, Isabelle Jacques, Nicolas Canu, Mireille Moutiez, Robert Thai, Muriel Gondry, Olivier Lequin, Pascal Belin
Prenylated indole diketopiperazine (DKP) alkaloids are important bioactive molecules or their precursors. In the context of synthetic biology, efficient means for their biological production would increase their chemical diversification and the discovery of novel bioactive compounds. Here, we prove the suitability of the Escherichia coli chassis for the production of prenylated indole DKP alkaloids. We used enzyme combinations not found in nature by co-expressing bacterial cyclodipeptide synthases (CDPSs) that assemble the DKP ring and fungal prenyltransferases (PTs) that transfer the allylic moiety from the dimethylallyl diphosphate (DMAPP) to the indole ring of tryptophanyl-containing cyclodipeptides...
June 25, 2019: Scientific Reports
https://read.qxmd.com/read/31206992/guanitrypmycin-biosynthetic-pathways-imply-cytochrome-p450-mediated-regio-and-stereospecific-guaninyl-transfer-reactions
#26
JOURNAL ARTICLE
Jing Liu, Xiulan Xie, Shu-Ming Li
Mining microbial genomes including those of Streptomyces reveals the presence of a large number of biosynthetic gene clusters. Unraveling this genetic potential was proven to be a useful approach for novel compound discovery. Here, we report the heterologous expression of two similar P450-associated cyclodipeptide synthases-containing gene clusters in Streptomyces coelicolor and identification of eight rare and novel natural products, C3-guaninyl indole alkaloids guanitrypmycins. Expression of different gene combinations proved that the cyclodipeptide synthases assemble cyclo-L-Trp-L-Phe and cyclo-L-Trp-L-Tyr, which are consecutively and regiospecifically modified by cyclodipeptide oxidases, cytochrome P450 enzymes, and N-methyltransferases...
June 17, 2019: Angewandte Chemie
https://read.qxmd.com/read/30688950/the-expanding-spectrum-of-diketopiperazine-natural-product-biosynthetic-pathways-containing-cyclodipeptide-synthases
#27
REVIEW
Paul Borgman, Ryan D Lopez, Amy L Lane
Microorganisms are remarkable chemists, with enzymes as their tools for executing multi-step syntheses to yield myriad natural products. Microbial synthetic aptitudes are illustrated by the structurally diverse 2,5-diketopiperazine (DKP) family of bioactive nonribosomal peptide natural products. Nonribosomal peptide synthetases (NRPSs) have long been recognized as catalysts for formation of DKP scaffolds from two amino acid substrates. Cyclodipeptide synthases (CDPSs) are more recently recognized catalysts of DKP assembly, employing two aminoacyl-tRNAs (aa-tRNAs) as substrates...
January 28, 2019: Organic & Biomolecular Chemistry
https://read.qxmd.com/read/30291234/genome-mining-of-cyclodipeptide-synthases-unravels-unusual-trna-dependent-diketopiperazine-terpene-biosynthetic-machinery
#28
JOURNAL ARTICLE
Tingting Yao, Jing Liu, Zengzhi Liu, Tong Li, Huayue Li, Qian Che, Tianjiao Zhu, Dehai Li, Qianqun Gu, Wenli Li
Cyclodipeptide synthases (CDPSs) can catalyze the formation of two successive peptide bonds by hijacking aminoacyl-tRNAs from the ribosomal machinery resulting in diketopiperazines (DKPs). Here, three CDPS-containing loci (dmt1-3) are discovered by genome mining and comparative genome analysis of Streptomyces strains. Among them, CDPS DmtB1, encoded by the gene of dmt1 locus, can synthesize cyclo(L-Trp-L-Xaa) (with Xaa being Val, Pro, Leu, Ile, or Ala). Systematic mutagenesis experiments demonstrate the importance of the residues constituting substrate-binding pocket P1 for the incorporation of the second aa-tRNA in DmtB1...
October 5, 2018: Nature Communications
https://read.qxmd.com/read/29767273/correction-to-expanding-tryptophan-containing-cyclodipeptide-synthase-spectrum-by-identification-of-nine-members-from-streptomyces-strains
#29
Jing Liu, Huili Yu, Shu-Ming Li
The original version of this article contained mistake. After careful re-examination of the LC-MS data, the products of CDPSs "WP_031028810" and "BAU83478" should be cFL instead of cPY. We apologize for any inconvenience that this may have caused.
May 16, 2018: Applied Microbiology and Biotechnology
https://read.qxmd.com/read/29728603/cyclization-reaction-catalyzed-by-cyclodipeptide-synthases-relies-on-a-conserved-tyrosine-residue
#30
JOURNAL ARTICLE
Emmanuelle Schmitt, Gabrielle Bourgeois, Muriel Gondry, Alexey Aleksandrov
Cyclodipeptide synthases (CDPSs) form various cyclodipeptides from two aminoacyl tRNAs via a stepwise mechanism with the formation of a dipeptidyl enzyme intermediate. As a final step of the catalytic reaction, the dipeptidyl group undergoes intramolecular cyclization to generate the target cyclodipeptide product. In this work, we investigated the cyclization reaction in the cyclodipeptide synthase AlbC using QM/MM methods and free energy simulations. The results indicate that the catalytic Y202 residue is in its neutral protonated form, and thus, is not likely to serve as a general base during the reaction...
May 4, 2018: Scientific Reports
https://read.qxmd.com/read/29703732/regulation-of-the-synthesis-and-secretion-of-the-iron-chelator-cyclodipeptide-pulcherriminic-acid-in-bacillus-licheniformis
#31
JOURNAL ARTICLE
Dong Wang, Yangyang Zhan, Dongbo Cai, Xiaoyun Li, Qin Wang, Shouwen Chen
The cyclodipeptide pulcherriminic acid synthesized by Bacillus licheniformis is an iron chelator and antagonizes certain pathogens by removing iron from the environment. But as the insoluble Fe-pulcherriminic acid complex cannot act as an iron carrier like siderophores, so excessive synthesized pulcherriminic acid causes iron starvation for the producer cells. At present, regulation of pulcherriminic acid synthesis and the mechanism by which B. licheniformis strikes a balance between biocontrol and self-protection from excessive iron removal remain unclear...
April 27, 2018: Applied and Environmental Microbiology
https://read.qxmd.com/read/29574613/expanding-tryptophan-containing-cyclodipeptide-synthase-spectrum-by-identification-of-nine-members-from-streptomyces-strains
#32
JOURNAL ARTICLE
Jing Liu, Huili Yu, Shu-Ming Li
Cyclodipeptide synthases (CDPSs) comprise normally 200-300 amino acid residues and are mainly found in bacteria. They hijack aminoacyl-tRNAs from the ribosomal machinery for cyclodipeptide formation. In this study, nine new CDPS genes from eight Streptomyces strains were cloned into pET28a vector and expressed in Escherichia coli. Structural elucidation of the isolated products led to the identification of one cyclo-L-Trp-L-Leu, two cyclo-L-Trp-L-Pro, and three cyclo-L-Trp-L-Trp synthases. Other three CDPSs produce cyclo-L-Trp-L-Ala or cyclo-L-Trp-L-Tyr as the major cyclodipeptide...
May 2018: Applied Microbiology and Biotechnology
https://read.qxmd.com/read/29505829/structural-basis-for-partition-of-the-cyclodipeptide-synthases-into-two-subfamilies
#33
JOURNAL ARTICLE
Gabrielle Bourgeois, Jérôme Seguin, Morgan Babin, Pascal Belin, Mireille Moutiez, Yves Mechulam, Muriel Gondry, Emmanuelle Schmitt
Cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides that can be further used for the synthesis of diketopiperazines. It was shown that CDPSs fall into two subfamilies, NYH and XYP, characterized by the presence of specific sequence signatures. However, current understanding of CDPSs only comes from studies of enzymes from the NYH subfamily. The present study reveals the crystal structures of three CDPSs from the XYP subfamily. Comparison of the XYP and NYH enzymes shows that the two subfamilies mainly differ in the first half of their Rossmann fold...
July 2018: Journal of Structural Biology
https://read.qxmd.com/read/29500259/discovery-and-biosynthesis-of-the-antibiotic-bicyclomycin-in-distantly-related-bacterial-classes
#34
JOURNAL ARTICLE
Natalia M Vior, Rodney Lacret, Govind Chandra, Siobhán Dorai-Raj, Martin Trick, Andrew W Truman
Bicyclomycin (BCM) is a clinically promising antibiotic that is biosynthesized by Streptomyces cinnamoneus DSM 41675. BCM is structurally characterized by a core cyclo(l-Ile-l-Leu) 2,5-diketopiperazine (DKP) that is extensively oxidized. Here, we identify the BCM biosynthetic gene cluster, which shows that the core of BCM is biosynthesized by a cyclodipeptide synthase, and the oxidative modifications are introduced by five 2-oxoglutarate-dependent dioxygenases and one cytochrome P450 monooxygenase. The discovery of the gene cluster enabled the identification of BCM pathways encoded by the genomes of hundreds of Pseudomonas aeruginosa isolates distributed globally, and heterologous expression of the pathway from P...
May 1, 2018: Applied and Environmental Microbiology
https://read.qxmd.com/read/29483897/a-comprehensive-overview-of-the-cyclodipeptide-synthase-family-enriched-with-the-characterization-of-32-new-enzymes
#35
JOURNAL ARTICLE
Muriel Gondry, Isabelle B Jacques, Robert Thai, Morgan Babin, Nicolas Canu, Jérôme Seguin, Pascal Belin, Jean-Luc Pernodet, Mireille Moutiez
Cyclodipeptide synthases (CDPSs) use as substrates two amino acids activated as aminoacyl-tRNAs to synthesize cyclodipeptides in secondary metabolites biosynthetic pathways. Since the first description of a CDPS in 2002, the number of putative CDPSs in databases has increased exponentially, reaching around 800 in June 2017. They are likely to be involved in numerous biosynthetic pathways but the diversity of their products is still under-explored. Here, we describe the activity of 32 new CDPSs, bringing the number of experimentally characterized CDPSs to about 100...
2018: Frontiers in Microbiology
https://read.qxmd.com/read/29377457/incorporation-of-non-canonical-amino-acids-into-2-5-diketopiperazines-by-cyclodipeptide-synthases
#36
JOURNAL ARTICLE
Nicolas Canu, Pascal Belin, Robert Thai, Isabelle Correia, Olivier Lequin, Jérôme Seguin, Mireille Moutiez, Muriel Gondry
The manipulation of natural product biosynthetic pathways is a powerful means of expanding the chemical diversity of bioactive molecules. 2,5-diketopiperazines (2,5-DKPs) have been widely developed by medicinal chemists, but their biological production is yet to be exploited. We introduce an in vivo method for incorporating non-canonical amino acids (ncAAs) into 2,5-DKPs using cyclodipeptide synthases (CDPSs), the enzymes responsible for scaffold assembly in many 2,5-DKP biosynthetic pathways. CDPSs use aminoacyl-tRNAs as substrates...
March 12, 2018: Angewandte Chemie
https://read.qxmd.com/read/29334896/global-analysis-of-prokaryotic-trna-derived-cyclodipeptide-biosynthesis
#37
JOURNAL ARTICLE
Michael A Skinnider, Chad W Johnston, Nishanth J Merwin, Chris A Dejong, Nathan A Magarvey
BACKGROUND: Among naturally occurring small molecules, tRNA-derived cyclodipeptides are a class that have attracted attention for their diverse and desirable biological activities. However, no tools are available to link cyclodipeptide synthases identified within prokaryotic genome sequences to their chemical products. Consequently, it is unclear how many genetically encoded cyclodipeptides represent novel products, and which producing organisms should be targeted for discovery. RESULTS: We developed a pipeline for identification and classification of cyclodipeptide biosynthetic gene clusters and prediction of aminoacyl-tRNA substrates and complete chemical structures...
January 15, 2018: BMC Genomics
https://read.qxmd.com/read/29194897/a-six-oxidase-cascade-for-tandem-c-h-bond-activation-revealed-by-reconstitution-of-bicyclomycin-biosynthesis
#38
JOURNAL ARTICLE
Song Meng, Wei Han, Juan Zhao, Xiao-Hong Jian, Hai-Xue Pan, Gong-Li Tang
As a commercial antibiotic, bicyclomycin (BCM) is currently the only known natural product targeting the transcription termination factor rho. It belongs to a family of highly functionalized diketopiperazine (DKP) alkaloids and bears a unique O-bridged bicyclo[4.2.2]piperazinedione ring system, a C1 triol, and terminal exo-methylene groups. We have identified and characterized the BCM biosynthetic pathway by heterologous biotransformations, in vitro biochemical assays, and one-pot enzymatic synthesis. A tRNA-dependent cyclodipeptide synthase guides the heterodimerization of leucine and isoleucine to afford the DKP precursor; subsequently, six redox enzymes, including five α-ketoglutarate/Fe2+ -dependent dioxygenases and one cytochrome P450 monooxygenase, regio- and stereoselectively install four hydroxy groups (primary, secondary, and two tertiary), an exo-methylene moiety, and a medium-sized bridged ring through the functionalization of eight unactivated C-H bonds...
January 15, 2018: Angewandte Chemie
https://read.qxmd.com/read/29065531/cyclodipeptides-an-overview-of-their-biosynthesis-and-biological-activity
#39
REVIEW
Awdhesh Kumar Mishra, Jaehyuk Choi, Seong-Jin Choi, Kwang-Hyun Baek
Cyclodipeptides (CDP) represent a diverse family of small, highly stable, cyclic peptides that are produced as secondary functional metabolites or side products of protein metabolism by bacteria, fungi, and animals. They are widespread in nature, and exhibit a broad variety of biological and pharmacological activities. CDP synthases (CDPSs) and non-ribosomal peptide synthetases (NRPSs) catalyze the biosynthesis of the CDP core structure, which is further modified by tailoring enzymes often associated with CDP biosynthetic gene clusters...
October 23, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/29064250/mutations-of-residues-in-pocket-p1-of-a-cyclodipeptide-synthase-strongly-increase-product-formation
#40
JOURNAL ARTICLE
Kirsten Brockmeyer, Shu-Ming Li
Expression of a cyclodipeptide synthase gene from Nocardiopsis prasina (CDPS-Np) in Escherichia coli resulted in the formation of cyclo-(l-Tyr-l-Tyr) (1) as the minor and cyclo-(l-Tyr-l-Phe) (2) as the major products. Site-directed mutagenesis revealed a strong influence on product accumulation of the amino acid residues in pocket P1. An 8-fold increase in product formation for 1 and 10-fold for 2 were detected in the double mutant T82V_Y196F compared with the wild type.
November 22, 2017: Journal of Natural Products
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