scholarly journals Diversity of Bacterial Biosynthetic Genes in Maritime Antarctica

2020 ◽  
Vol 8 (2) ◽  
pp. 279 ◽  
Author(s):  
Adriana Rego ◽  
António G. G. Sousa ◽  
João P. Santos ◽  
Francisco Pascoal ◽  
João Canário ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Polyketide Synthase ◽  
Amplicon Sequencing ◽  
Soil Samples ◽  
Chemical Diversity ◽  
Maritime Antarctica ◽  
Biosynthetic Genes ◽  
Peptide Synthetase ◽  
Drug Leads ◽  
Culture Dependent

Bacterial natural products (NPs) are still a major source of new drug leads. Polyketides (PKs) and non-ribosomal peptides (NRP) are two pharmaceutically important families of NPs and recent studies have revealed Antarctica to harbor endemic polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes, likely to be involved in the production of novel metabolites. Despite this, the diversity of secondary metabolites genes in Antarctica is still poorly explored. In this study, a computational bioprospection approach was employed to study the diversity and identity of PKS and NRPS genes to one of the most biodiverse areas in maritime Antarctica—Maxwell Bay. Amplicon sequencing of soil samples targeting ketosynthase (KS) and adenylation (AD) domains of PKS and NRPS genes, respectively, revealed abundant and unexplored chemical diversity in this peninsula. About 20% of AD domain sequences were only distantly related to characterized biosynthetic genes. Several PKS and NRPS genes were found to be closely associated to recently described metabolites including those from uncultured and candidate phyla. The combination of new approaches in computational biology and new culture-dependent and -independent strategies is thus critical for the recovery of the potential novel chemistry encoded in Antarctica microorganisms.

scholarly journals Polyketide Synthase and Nonribosomal Peptide Synthetase Gene Clusters in Type Strains of the Genus Phytohabitans

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 257
Author(s):  
Hisayuki Komaki ◽  
Tomohiko Tamura
Keyword(s):  
Secondary Metabolites ◽  
Polyketide Synthase ◽  
Gene Clusters ◽  
Nonribosomal Peptide Synthetase ◽  
Nrps Gene ◽  
Nonribosomal Peptide ◽  
Rare Actinomycetes ◽  
Whole Genomes ◽  
Peptide Synthetase ◽  
Established Genus

(1) Background: Phytohabitans is a recently established genus belonging to rare actinomycetes. It has been unclear if its members have the capacity to synthesize diverse secondary metabolites. Polyketide and nonribosomal peptide compounds are major secondary metabolites in actinomycetes and expected as a potential source for novel pharmaceuticals. (2) Methods: Whole genomes of Phytohabitans flavus NBRC 107702T, Phytohabitans rumicis NBRC 108638T, Phytohabitans houttuyneae NBRC 108639T, and Phytohabitans suffuscus NBRC 105367T were sequenced by PacBio. Polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) gene clusters were bioinformatically analyzed in the genome sequences. (3) Results: These four strains harbored 10, 14, 18 and 14 PKS and NRPS gene clusters, respectively. Most of the gene clusters were annotated to synthesis unknown chemistries. (4) Conclusions: Members of the genus Phytohabitans are a possible source for novel and diverse polyketides and nonribosomal peptides.

scholarly journals Avant-garde assembly-line biosynthesis expands diversity of cyclic lipodepsipeptide products

2019 ◽  
Author(s):  
Jia Jia Zhang ◽  
Xiaoyu Tang ◽  
Tao Huan ◽  
Avena C. Ross ◽  
Bradley S. Moore
Keyword(s):  
Assembly Line ◽  
Polyketide Synthase ◽  
Structural Features ◽  
Chemical Diversity ◽  
Chain Extension ◽  
Assembly Lines ◽  
Avant Garde ◽  
Peptide Synthetase ◽  
Domain Interactions ◽  
Catalytic Cycles

Modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzymatic assembly lines are large and dynamic protein machines that generally undergo a linear progression of catalytic cycles via a series of enzymatic domains organized into independent modules. Here we report the heterologous reconstitution and comprehensive characterization of two hybrid NRPS-PKS assembly lines that defy many standard rules of assembly-line biosynthesis to generate a large combinatorial library of cyclic lipodepsipeptide protease inhibitors called thalassospiramides. We generate a series of precise domain-inactivating mutations in thalassospiramide assembly lines and present compelling evidence for an unprecedented biosynthetic model that invokes inter-module substrate activation and tailoring, module skipping, and pass-back chain extension, whereby the ability to pass the growing chain back to a preceding module is flexible and substrate-driven. Expanding bidirectional inter-module domain interactions could represent a viable mechanism for generating chemical diversity without increasing the size of biosynthetic assembly lines and raises new questions regarding our understanding of the structural features of multi-modular megaenzymes.

scholarly journals Moorea producens gen. nov., sp. nov. and Moorea bouillonii comb. nov., tropical marine cyanobacteria rich in bioactive secondary metabolites

2012 ◽  
Vol 62 (Pt_5) ◽  
pp. 1171-1178 ◽  
Author(s):  
Niclas Engene ◽  
Erin C. Rottacker ◽  
Jan Kaštovský ◽  
Tara Byrum ◽  
Hyukjae Choi ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Polyketide Synthase ◽  
Botanical Nomenclature ◽  
Distinctive Character ◽  
Content Type ◽  
Algae Blooms ◽  
Rich Diversity ◽  
Peptide Synthetase ◽  
Bioactive Secondary Metabolites ◽  
Micro Organisms

The filamentous cyanobacterial genus Moorea gen. nov., described here under the provisions of the International Code of Botanical Nomenclature, is a cosmopolitan pan-tropical group abundant in the marine benthos. Members of the genus Moorea are photosynthetic (containing phycocyanin, phycoerythrin, allophycocyanin and chlorophyll a), but non-diazotrophic (lack heterocysts and nitrogenase reductase genes). The cells (discoid and 25–80 µm wide) are arranged in long filaments (<10 cm in length) and often form extensive mats or blooms in shallow water. The cells are surrounded by thick polysaccharide sheaths covered by a rich diversity of heterotrophic micro-organisms. A distinctive character of this genus is its extraordinarily rich production of bioactive secondary metabolites. This is matched by genomes rich in polyketide synthase and non-ribosomal peptide synthetase biosynthetic genes which are dedicated to secondary metabolism. The encoded natural products are sometimes responsible for harmful algae blooms and, due to morphological resemblance to the genus Lyngbya , this group has often been incorrectly cited in the literature. We here describe two species of the genus Moorea: Moorea producens sp. nov. (type species of the genus) with 3LT as the nomenclature type, and Moorea bouillonii comb. nov. with PNG5-198R as the nomenclature type.

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.

scholarly journals Meroterpenoids: A Comprehensive Update Insight on Structural Diversity and Biology

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 957
Author(s):  
Mamona Nazir ◽  
Muhammad Saleem ◽  
Muhammad Imran Tousif ◽  
Muhammad Aijaz Anwar ◽  
Frank Surup ◽  
...  
Keyword(s):  
Amino Acids ◽  
Secondary Metabolites ◽  
Biological Effects ◽  
Structural Diversity ◽  
Chemical Diversity ◽  
Biosynthetic Pathways ◽  
Natural Sources ◽  
Hybrid Compounds ◽  
Anti Inflammatory

Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.

scholarly journals Tetrodotoxins (TTXs) and Vibrio alginolyticus in Mussels from Central Adriatic Sea (Italy): Are They Closely Related?

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 304
Author(s):  
Simone Bacchiocchi ◽  
Debora Campacci ◽  
Melania Siracusa ◽  
Alessandra Dubbini ◽  
Francesca Leoni ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mytilus Galloprovincialis ◽  
Polyketide Synthase ◽  
Adriatic Sea ◽  
Tandem Mass ◽  
Hydrophilic Interaction ◽  
Marche Region ◽  
Peptide Synthetase ◽  
Scientific Opinion ◽  
Vibrio Spp

Tetrodotoxins (TTXs), potent neurotoxins, have become an increasing concern in Europe in recent decades, especially because of their presence in mollusks. The European Food Safety Authority published a Scientific Opinion setting a recommended threshold for TTX in mollusks of 44 µg equivalent kg−1 and calling all member states to contribute to an effort to gather data in order to produce a more exhaustive risk assessment. The objective of this work was to assess TTX levels in wild and farmed mussels (Mytilus galloprovincialis) harvested in 2018–2019 along the coastal area of the Marche region in the Central Adriatic Sea (Italy). The presence of Vibrio spp. carrying the non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) genes, which are suspected to be involved in TTX biosynthesis, was also investigated. Out of 158 mussel samples analyzed by hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry (HILIC-MS/MS), 11 (7%) contained the toxins at detectable levels (8–26 µg kg−1) and 3 (2%) contained levels above the EFSA safety threshold (61–76 µg kg−1). Contaminated mussels were all harvested from natural beds in spring or summer. Of the 2019 samples, 70% of them contained V. alginolyticus strains with the NRPS and/or PKS genes. None of the strains containing NRPS and/or PKS genes showed detectable levels of TTXs. TTXs in mussels are not yet a threat in the Marche region nor in Europe, but further investigations are surely needed.

scholarly journals Chemical Diversity and Bioactivities of Monoterpene Indole Alkaloids (MIAs) from Six Apocynaceae Genera

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 488
Author(s):  
Afrah E. Mohammed ◽  
Zainab H. Abdul-Hameed ◽  
Modhi O. Alotaibi ◽  
Nahed O. Bawakid ◽  
Tariq R. Sobahi ◽  
...  
Keyword(s):  
Biological Activities ◽  
Indole Alkaloids ◽  
Natural Compounds ◽  
Molecular Target ◽  
Chemical Diversity ◽  
Drug Lead ◽  
The Family ◽  
Monoterpene Indole Alkaloids ◽  
Drug Leads ◽  
Anti Hiv

By the end of the twentieth century, the interest in natural compounds as probable sources of drugs has declined and was replaced by other strategies such as molecular target-based drug discovery. However, in the recent times, natural compounds regained their position as extremely important source drug leads. Indole-containing compounds are under clinical use which includes vinblastine and vincristine (anticancer), atevirdine (anti-HIV), yohimbine (erectile dysfunction), reserpine (antihypertension), ajmalicine (vascular disorders), ajmaline (anti-arrhythmic), vincamine (vasodilator), etc. Monoterpene Indole Alkaloids (MIAs) deserve the curiosity and attention of researchers due to their chemical diversity and biological activities. These compounds were considered as an impending source of drug-lead. In this review 444 compounds, were identified from six genera belonging to the family Apocynaceae, will be discussed. These genera (Alstonia, Rauvolfia, Kopsia, Ervatamia, and Tabernaemontana, and Rhazya) consist of 400 members and represent 20% of Apocynaceae species. Only 30 (7.5%) species were investigated, whereas the rest are promising to be investigated. Eleven bioactivities, including antibacterial, antifungal, anti-inflammatory and immunosuppressant activities, were reported. Whereas cytotoxic effect represents 47% of the reported activities. Convincingly, the genera selected in this review are a wealthy source for future anticancer drug lead.

scholarly journals Chemical Diversity and Biological Activity of Secondary Metabolites from Soft Coral Genus Sinularia since 2013

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 335
Author(s):  
Xia Yan ◽  
Jing Liu ◽  
Xue Leng ◽  
Han Ouyang
Keyword(s):  
Biological Activity ◽  
Secondary Metabolites ◽  
Coral Species ◽  
Soft Coral ◽  
Biological Activities ◽  
Vital Role ◽  
Chemical Diversity ◽  
Pharmacological Activities ◽  
Lead Compounds ◽  
Coral Genus

Sinularia is one of the conspicuous soft coral species widely distributed in the world’s oceans at a depth of about 12 m. Secondary metabolites from the genus Sinularia show great chemical diversity. More than 700 secondary metabolites have been reported to date, including terpenoids, norterpenoids, steroids/steroidal glycosides, and other types. They showed a broad range of potent biological activities. There were detailed reviews on the terpenoids from Sinularia in 2013, and now, it still plays a vital role in the innovation of lead compounds for drug development. The structures, names, and pharmacological activities of compounds isolated from the genus Sinularia from 2013 to March 2021 are summarized in this review.

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