scholarly journals Inside Cover: Solanapyrone Synthase, a Possible Diels-Alderase and Iterative Type I Polyketide Synthase Encoded in a Biosynthetic Gene Cluster from Alternaria solani (ChemBioChem 9/2010)

ChemBioChem ◽  
2010 ◽  
Vol 11 (9) ◽  
pp. 1154-1154
Author(s):  
Ken Kasahara ◽  
Takanori Miyamoto ◽  
Takashi Fujimoto ◽  
Hiroki Oguri ◽  
Tetsuo Tokiwano ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Polyketide Synthase ◽  
Alternaria Solani ◽  
Biosynthetic Gene Cluster ◽  
Type I ◽  
Biosynthetic Gene

Solanapyrone Synthase, a Possible Diels-Alderase and Iterative Type I Polyketide Synthase Encoded in a Biosynthetic Gene Cluster from Alternaria solani

ChemBioChem ◽  
2010 ◽  
Vol 11 (9) ◽  
pp. 1245-1252 ◽  
Author(s):  
Ken Kasahara ◽  
Takanori Miyamoto ◽  
Takashi Fujimoto ◽  
Hiroki Oguri ◽  
Tetsuo Tokiwano ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Polyketide Synthase ◽  
Alternaria Solani ◽  
Biosynthetic Gene Cluster ◽  
Type I ◽  
Biosynthetic Gene

scholarly journals Genome Sequence-Guided Finding of Lucensomycin Production by Streptomyces achromogenes Subsp. streptozoticus NBRC14001

2021 ◽  
Vol 10 (1) ◽  
pp. 37
Author(s):  
Sho Nishimura ◽  
Kazune Nakamura ◽  
Miyako Yamamoto ◽  
Daichi Morita ◽  
Teruo Kuroda ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Gene Cluster ◽  
Genome Sequence ◽  
Polyketide Synthase ◽  
Macrolide Antibiotic ◽  
Biosynthetic Gene Cluster ◽  
Antifungal Compound ◽  
Type I ◽  
Biosynthetic Gene ◽  
Polyketide Synthase Gene

Information on microbial genome sequences is a powerful resource for accessing natural products with significant activities. We herein report the unveiling of lucensomycin production by Streptomyces achromogenes subsp. streptozoticus NBRC14001 based on the genome sequence of the strain. The genome sequence of strain NBRC14001 revealed the presence of a type I polyketide synthase gene cluster with similarities to a biosynthetic gene cluster for natamycin, which is a polyene macrolide antibiotic that exhibits antifungal activity. Therefore, we investigated whether strain NBRC14001 produces antifungal compound(s) and revealed that an extract from the strain inhibited the growth of Candida albicans. A HPLC analysis of a purified compound exhibiting antifungal activity against C. albicans showed that the compound differed from natamycin. Based on HR-ESI-MS spectrometry and a PubChem database search, the compound was predicted to be lucensomycin, which is a tetraene macrolide antibiotic, and this prediction was supported by the results of a MS/MS analysis. Furthermore, the type I polyketide synthase gene cluster in strain NBRC14001 corresponded well to lucesomycin biosynthetic gene cluster (lcm) in S. cyanogenus, which was very recently reported. Therefore, we concluded that the antifungal compound produced by strain NBRC14001 is lucensomycin.

scholarly journals Microfluidic automated plasmid library enrichment for biosynthetic gene cluster discovery

2020 ◽  
Vol 48 (8) ◽  
pp. e48-e48 ◽  
Author(s):  
Peng Xu ◽  
Cyrus Modavi ◽  
Benjamin Demaree ◽  
Frederick Twigg ◽  
Benjamin Liang ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Polyketide Synthase ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Bioactive Molecules ◽  
Type I ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Plasmid Library ◽  
Polyketide Synthase Gene

Abstract Microbial biosynthetic gene clusters are a valuable source of bioactive molecules. However, because they typically represent a small fraction of genomic material in most metagenomic samples, it remains challenging to deeply sequence them. We present an approach to isolate and sequence gene clusters in metagenomic samples using microfluidic automated plasmid library enrichment. Our approach provides deep coverage of the target gene cluster, facilitating reassembly. We demonstrate the approach by isolating and sequencing type I polyketide synthase gene clusters from an Antarctic soil metagenome. Our method promotes the discovery of functional-related genes and biosynthetic pathways.

scholarly journals Glycosylation Steps during Spiramycin Biosynthesis in Streptomyces ambofaciens: Involvement of Three Glycosyltransferases and Their Interplay with Two Auxiliary Proteins

2010 ◽  
Vol 54 (7) ◽  
pp. 2830-2839 ◽  
Author(s):  
Hoang Chuong Nguyen ◽  
Fatma Karray ◽  
Sylvie Lautru ◽  
Josette Gagnat ◽  
Ahmed Lebrihi ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Polyketide Synthase ◽  
Macrolide Antibiotic ◽  
Biosynthetic Gene Cluster ◽  
Type I ◽  
Biosynthetic Gene ◽  
Streptomyces Ambofaciens ◽  
Mutant Strains ◽  
Genes Encoding

ABSTRACT Streptomyces ambofaciens synthesizes spiramycin, a 16-membered macrolide antibiotic used in human medicine. The spiramycin molecule consists of a polyketide lactone ring (platenolide) synthesized by a type I polyketide synthase, to which three deoxyhexoses (mycaminose, forosamine, and mycarose) are attached successively in this order. These sugars are essential to the antibacterial activity of spiramycin. We previously identified four genes in the spiramycin biosynthetic gene cluster predicted to encode glycosyltransferases. We individually deleted each of these four genes and showed that three of them were required for spiramycin biosynthesis. The role of each of the three glycosyltransferases in spiramycin biosynthesis was determined by identifying the biosynthetic intermediates accumulated by the corresponding mutant strains. This led to the identification of the glycosyltransferase responsible for the attachment of each of the three sugars. Moreover, two genes encoding putative glycosyltransferase auxiliary proteins were also identified in the spiramycin biosynthetic gene cluster. When these two genes were deleted, one of them was found to be dispensable for spiramycin biosynthesis. However, analysis of the biosynthetic intermediates accumulated by mutant strains devoid of each of the auxiliary proteins (or of both of them), together with complementation experiments, revealed the interplay of glycosyltransferases with the auxiliary proteins. One of the auxiliary proteins interacted efficiently with the two glycosyltransferases transferring mycaminose and forosamine while the other auxiliary protein interacted only with the mycaminosyltransferase.

scholarly journals Identification and Heterologous Expression of the Kendomycin B Biosynthetic Gene Cluster from Verrucosispora sp. SCSIO 07399

Marine Drugs ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. 673
Author(s):  
Jiang Chen ◽  
Shanwen Zhang ◽  
Yingying Chen ◽  
Xinpeng Tian ◽  
Yucheng Gu ◽  
...  
Keyword(s):  
Heterologous Expression ◽  
Gene Cluster ◽  
Polyketide Synthase ◽  
Regulatory Gene ◽  
Biosynthetic Gene Cluster ◽  
Chain Elongation ◽  
Type I ◽  
Biosynthetic Gene ◽  
Type Iii Polyketide Synthase ◽  
Type Iii

Verrucosispora sp. SCSIO 07399, a rare marine-derived actinomycete, produces a set of ansamycin-like polyketides kendomycin B–D (1–3) which possess potent antibacterial activities and moderate tumor cytotoxicity. Structurally, kendomycin B–D contain a unique aliphatic macrocyclic ansa scaffold in which the highly substituted pyran ring is connected to the quinone moiety. In this work, a type I/type III polyketide synthase (PKS) hybrid biosynthetic gene cluster coding for assembly of kendomycin B (kmy), and covering 33 open reading frames, was identified from Verrucosispora sp. SCSIO 07399. The kmy cluster was found to be essential for kendomycin B biosynthesis as verified by gene disruption and heterologous expression. Correspondingly, a biosynthetic pathway was proposed based on bioinformatics, cluster alignments, and previous research. Additionally, the role of type III PKS for generating the precursor unit 3,5-dihydroxybenzoic acid (3,5-DHBA) was demonstrated by chemical complementation, and type I PKS executed the polyketide chain elongation. The kmy cluster was found to contain a positive regulatory gene kmy4 whose regulatory effect was identified using real-time quantitative PCR (RT-qPCR). These advances shed important new insights into kendomycin B biosynthesis and help to set the foundation for further research aimed at understanding and exploiting the carbacylic ansa scaffold.

scholarly journals Characterization of the Nodularin Synthetase Gene Cluster and Proposed Theory of the Evolution of Cyanobacterial Hepatotoxins

2004 ◽  
Vol 70 (11) ◽  
pp. 6353-6362 ◽  
Author(s):  
Michelle C. Moffitt ◽  
Brett A. Neilan
Keyword(s):  
Gene Cluster ◽  
Rational Design ◽  
Polyketide Synthase ◽  
Alternative Hypothesis ◽  
Phylogenetic Analyses ◽  
Cyanobacterial Bloom ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Microcystin Synthetase

ABSTRACT Nodularia spumigena is a bloom-forming cyanobacterium which produces the hepatotoxin nodularin. The complete gene cluster encoding the enzymatic machinery required for the biosynthesis of nodularin in N. spumigena strain NSOR10 was sequenced and characterized. The 48-kb gene cluster consists of nine open reading frames (ORFs), ndaA to ndaI, which are transcribed from a bidirectional regulatory promoter region and encode nonribosomal peptide synthetase modules, polyketide synthase modules, and tailoring enzymes. The ORFs flanking the nda gene cluster in the genome of N. spumigena strain NSOR10 were identified, and one of them was found to encode a protein with homology to previously characterized transposases. Putative transposases are also associated with the structurally related microcystin synthetase (mcy) gene clusters derived from three cyanobacterial strains, indicating a possible mechanism for the distribution of these biosynthetic gene clusters between various cyanobacterial genera. We propose an alternative hypothesis for hepatotoxin evolution in cyanobacteria based on the results of comparative and phylogenetic analyses of the nda and mcy gene clusters. These analyses suggested that nodularin synthetase evolved from a microcystin synthetase progenitor. The identification of the nodularin biosynthetic gene cluster and evolution of hepatotoxicity in cyanobacteria reported in this study may be valuable for future studies on toxic cyanobacterial bloom formation. In addition, an appreciation of the natural evolution of nonribosomal biosynthetic pathways will be vital for future combinatorial engineering and rational design of novel metabolites and pharmaceuticals.

scholarly journals Characterization of a Gene Cluster Responsible for the Biosynthesis of Anticancer Agent FK228 in Chromobacterium violaceum No. 968

2007 ◽  
Vol 73 (11) ◽  
pp. 3460-3469 ◽  
Author(s):  
Yi-Qiang Cheng ◽  
Min Yang ◽  
Andrea M. Matter
Keyword(s):  
Gene Cluster ◽  
Genomic Dna ◽  
Polyketide Synthase ◽  
Anticancer Agent ◽  
Biosynthetic Gene Cluster ◽  
Nonribosomal Peptide Synthetase ◽  
Biosynthetic Gene ◽  
Biosynthetic Genes ◽  
Nonribosomal Peptide ◽  
Peptide Synthetase

ABSTRACT A gene cluster responsible for the biosynthesis of anticancer agent FK228 has been identified, cloned, and partially characterized in Chromobacterium violaceum no. 968. First, a genome-scanning approach was applied to identify three distinctive C. violaceum no. 968 genomic DNA clones that code for portions of nonribosomal peptide synthetase and polyketide synthase. Next, a gene replacement system developed originally for Pseudomonas aeruginosa was adapted to inactivate the genomic DNA-associated candidate natural product biosynthetic genes in vivo with high efficiency. Inactivation of a nonribosomal peptide synthetase-encoding gene completely abolished FK228 production in mutant strains. Subsequently, the entire FK228 biosynthetic gene cluster was cloned and sequenced. This gene cluster is predicted to encompass a 36.4-kb DNA region that includes 14 genes. The products of nine biosynthetic genes are proposed to constitute an unusual hybrid nonribosomal peptide synthetase-polyketide synthase-nonribosomal peptide synthetase assembly line including accessory activities for the biosynthesis of FK228. In particular, a putative flavin adenine dinucleotide-dependent pyridine nucleotide-disulfide oxidoreductase is proposed to catalyze disulfide bond formation between two sulfhydryl groups of cysteine residues as the final step in FK228 biosynthesis. Acquisition of the FK228 biosynthetic gene cluster and acclimation of an efficient genetic system should enable genetic engineering of the FK228 biosynthetic pathway in C. violaceum no. 968 for the generation of structural analogs as anticancer drug candidates.

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