scholarly journals Linking Genes to Molecules in Eukaryotic Sources: An Endeavor to Expand Our Biosynthetic Repertoire

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 625
Author(s):  
Jack G. Ganley ◽  
Emily R. Derbyshire
Keyword(s):  
Small Molecules ◽  
Natural Product ◽  
Biosynthetic Gene Cluster ◽  
Compelling Evidence ◽  
Biosynthetic Gene ◽  
Guided Discovery ◽  
Natural Product Discovery ◽  
Chemical Structures ◽  
Synthetic Utility ◽  
Fungal Genomes

The discovery of natural products continues to interest chemists and biologists for their utility in medicine as well as facilitating our understanding of signaling, pathogenesis, and evolution. Despite an attenuation in the discovery rate of new molecules, the current genomics and transcriptomics revolution has illuminated the untapped biosynthetic potential of many diverse organisms. Today, natural product discovery can be driven by biosynthetic gene cluster (BGC) analysis, which is capable of predicting enzymes that catalyze novel reactions and organisms that synthesize new chemical structures. This approach has been particularly effective in mining bacterial and fungal genomes where it has facilitated the discovery of new molecules, increased the understanding of metabolite assembly, and in some instances uncovered enzymes with intriguing synthetic utility. While relatively less is known about the biosynthetic potential of non-fungal eukaryotes, there is compelling evidence to suggest many encode biosynthetic enzymes that produce molecules with unique bioactivities. In this review, we highlight how the advances in genomics and transcriptomics have aided natural product discovery in sources from eukaryotic lineages. We summarize work that has successfully connected genes to previously identified molecules and how advancing these techniques can lead to genetics-guided discovery of novel chemical structures and reactions distributed throughout the tree of life. Ultimately, we discuss the advantage of increasing the known biosynthetic space to ease access to complex natural and non-natural small molecules.

scholarly journals New Insights into the Genetic Organization of the FK228 Biosynthetic Gene Cluster inChromobacterium violaceumNo. 968

2010 ◽  
Vol 77 (4) ◽  
pp. 1508-1511 ◽  
Author(s):  
Vishwakanth Y. Potharla ◽  
Shane R. Wesener ◽  
Yi-Qiang Cheng
Keyword(s):  
Natural Product ◽  
Gene Cluster ◽  
Gene Deletion ◽  
Regulatory Gene ◽  
Biosynthetic Gene Cluster ◽  
Transcriptional Analysis ◽  
Biosynthetic Gene ◽  
Genetic Organization

ABSTRACTThe biosynthetic gene cluster of FK228, an FDA-approved anticancer natural product, was identified and sequenced previously. The genetic organization of this gene cluster has now been delineated through systematic gene deletion and transcriptional analysis. As a result, the gene cluster is redefined to contain 12 genes:depAthroughdepJ,depM, and a newly identified pathway regulatory gene,depR.

scholarly journals Bioactive Molecules from Mangrove Streptomyces qinglanensis 172205

Marine Drugs ◽  
2020 ◽  
Vol 18 (5) ◽  
pp. 255
Author(s):  
Dongbo Xu ◽  
Erli Tian ◽  
Fandong Kong ◽  
Kui Hong
Keyword(s):  
Gene Cluster ◽  
Secondary Metabolite ◽  
Biosynthetic Gene Cluster ◽  
Bioactive Molecules ◽  
Spectroscopic Methods ◽  
Biosynthetic Gene ◽  
Electronic Circular Dichroism ◽  
Chemical Structures ◽  
New Compounds ◽  
Antiproliferative Activities

Five new compounds 15R-17,18-dehydroxantholipin (1), (3E,5E,7E)-3-methyldeca-3,5,7-triene-2,9-dione (2) and qinlactone A–C (3–5) were identified from mangrove Streptomyces qinglanensis 172205 with “genetic dereplication,” which deleted the highly expressed secondary metabolite-enterocin biosynthetic gene cluster. The chemical structures were established by spectroscopic methods, and the absolute configurations were determined by electronic circular dichroism (ECD). Compound 1 exhibited strong anti-microbial and antiproliferative bioactivities, while compounds 2–4 showed weak antiproliferative activities.

scholarly journals Genomic Assemblies of Members of Burkholderia and Related Genera as a Resource for Natural Product Discovery

2020 ◽  
Vol 9 (42) ◽  
Author(s):  
Alex J. Mullins ◽  
Cerith Jones ◽  
Matthew J. Bull ◽  
Gordon Webster ◽  
Julian Parkhill ◽  
...  
Keyword(s):  
Natural Product ◽  
Genome Mining ◽  
Genomic Analysis ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Natural Product Discovery

ABSTRACT The genomes of 450 members of Burkholderiaceae, isolated from clinical and environmental sources, were sequenced and assembled as a resource for genome mining. Genomic analysis of the collection has enabled the identification of multiple metabolites and their biosynthetic gene clusters, including the antibiotics gladiolin, icosalide A, enacyloxin, and cepacin A.

scholarly journals mSphere of Influence: Synthetic Biology of Natural Product Biosynthesis

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Mark C. Walker
Keyword(s):  
Natural Products ◽  
Synthetic Biology ◽  
Natural Product ◽  
Gene Cluster ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Natural Product Biosynthesis ◽  
Antibiotic Compounds ◽  
Approaches To Study

ABSTRACT Mark Walker studies the biosynthesis and engineering of bacterial natural products with the long-term goal of identifying new antibiotic compounds. In this mSphere of Influence, he reflects on how “Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A” by K. Yamanaka, K. A. Reynolds, R. D. Kersten, K. S. Ryan, et al. (Proc Natl Acad Sci USA 111:1957–1962, 2014, https://doi.org/10.1073/pnas.1319584111) impacted his thinking on using synthetic biology approaches to study natural product biosynthesis.

Alkynyl Prins and Alkynyl Aza-Prins Annulations: Scope and Synthetic Applications

Synthesis ◽  
2020 ◽  
Vol 52 (14) ◽  
pp. 1991-2007 ◽  
Author(s):  
Alison J. Frontier ◽  
Shukree Abdul-Rashed ◽  
Connor Holt
Keyword(s):  
Natural Products ◽  
Small Molecules ◽  
Natural Product ◽  
Natural Product Synthesis ◽  
Pericyclic Reactions ◽  
Prins Reaction ◽  
Prins Cyclization ◽  
Synthetic Utility ◽  
Cascade Processes ◽  
Saturated Heterocycles

This review focuses on alkynyl Prins and alkynyl aza-Prins cyclization­ processes, which involve intramolecular coupling of an alkyne with either an oxocarbenium or iminium electrophile. The oxocarbenium or iminium species can be generated through condensation- or elimination-type processes, to achieve an overall bimolecular annulation that enables the synthesis of both oxygen- and nitrogen-containing­ saturated heterocycles with different ring sizes and substitution patterns. Also discussed are cascade processes in which alkynyl Prins heterocyclic adducts react to trigger subsequent pericyclic reactions, including [4+2] cycloadditions and Nazarov electrocyclizations, to rapidly construct complex small molecules. Finally, examples of the use of alkynyl Prins and alkynyl aza-Prins reactions in the synthesis of natural products are described. The review covers the literature through the end of 2019.1 Introduction1.1 Alkyne-Carbonyl Coupling Pathways1.2 Coupling/Cyclization Cascades Using the Alkynyl Prins Reaction2 Alkynyl Prins Annulation (Oxocarbenium Electrophiles)2.1 Early Work2.2 Halide as Terminal Nucleophile2.3 Oxygen as Terminal Nucleophile2.4 Arene as Terminal Nucleophile (Intermolecular)2.5 Arene Terminal Nucleophile (Intramolecular)2.6 Cyclizations Terminated by Elimination3 Synthetic Utility of Alkynyl Prins Annulation3.1 Alkynyl Prins-Mediated Synthesis of Dienes for a [4+2] Cyclo­- addition­-Oxidation Sequence3.2 Alkynyl Prins Cyclization Adducts as Nazarov Cyclization Precursors3.3 Alkynyl Prins Cyclization in Natural Product Synthesis4 Alkynyl Aza-Prins Annulation4.1 Iminium Electrophiles4.2 Activated Iminium Electrophiles5 Alkynyl Aza-Prins Cyclizations in Natural Product Synthesis6 Summary and Outlook

scholarly journals Tracking Down Biotransformation to the Genetic Level: Identification of a Highly Flexible Glycosyltransferase from Saccharothrix espanaensis

2013 ◽  
Vol 79 (17) ◽  
pp. 5224-5232 ◽  
Author(s):  
Tina Strobel ◽  
Yvonne Schmidt ◽  
Anton Linnenbrink ◽  
Andriy Luzhetskyy ◽  
Marta Luzhetska ◽  
...  
Keyword(s):  
Natural Products ◽  
Phenolic Compounds ◽  
Natural Product ◽  
Defense Mechanism ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Gene Encoding ◽  
Content Type ◽  
Genetic Level ◽  
Level Identification

ABSTRACTSaccharothrix espanaensisis a member of the orderActinomycetales. The genome of the strain has been sequenced recently, revealing 106 glycosyltransferase genes. In this paper, we report the detection of a glycosyltransferase fromSaccharothrix espanaensiswhich is able to rhamnosylate different phenolic compounds targeting different positions of the molecules. The gene encoding the flexible glycosyltransferase is not located close to a natural product biosynthetic gene cluster. Therefore, the native function of this enzyme might be not the biosynthesis of a secondary metabolite but the glycosylation of internal and external natural products as part of a defense mechanism.

scholarly journals Conservation of griseofulvin genes in the gsf gene cluster among fungal genomes

2021 ◽  
Author(s):  
Parisa Aris ◽  
Lihong Yan ◽  
Yulong Wei ◽  
Ying Chang ◽  
Bihong Shi ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Biosynthetic Gene Cluster ◽  
Fungal Species ◽  
Antifungal Compound ◽  
Biosynthetic Gene ◽  
Polyketide Biosynthesis ◽  
Third Generation Sequencing ◽  
Penicillium Griseofulvum ◽  
Fungal Genomes ◽  
Generation Sequencing

Abstract The polyketide griseofulvin is a natural antifungal compound and research in griseofulvin has been key in establishing our current understanding of polyketide biosynthesis. Nevertheless, the griseofulvin gsf biosynthetic gene cluster (BGC) remains poorly understood in most fungal species, including Penicillium griseofulvum where griseofulvin was first isolated. To elucidate essential genes involved in griseofulvin biosynthesis, we performed third-generation sequencing to obtain the genome of Penicillium griseofulvum strain D-756. Furthermore, we gathered publicly available genome of 11 other fungal species in which gsf gene cluster was identified. In a comparative genome analysis, we annotated and compared the gsf BGC of all 12 fungal genomes. Our findings show no gene rearrangements at the gsf BGC. Furthermore, seven gsf genes are conserved by most genomes surveyed whereas the remaining six were poorly conserved. This study provides new insights into differences between gsf BGC and suggests that seven gsf genes are essential in griseofulvin production.

scholarly journals Qinichelins, novel catecholate-hydroxamate siderophores synthesized via a multiplexed convergent biosynthesis pathway

2017 ◽  
Author(s):  
Jacob Gubbens ◽  
Changsheng Wu ◽  
Hua Zhu ◽  
Dmitri V. Filippov ◽  
Bogdan I. Florea ◽  
...  
Keyword(s):  
Natural Product ◽  
Expression Profiles ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Chemical Diversity ◽  
Orphan Gene ◽  
Natural Product Discovery ◽  
Bioinformatic Tools ◽  
Hydroxamate Siderophores ◽  
Protein Expression Profiles

ABSTRACTThe explosive increase in genome sequencing and the advances in bioinformatic tools have revolutionized the rationale for natural product discovery from actinomycetes. In particular, this has revealed that actinomycete genomes contain numerous orphan gene clusters that have the potential to specify many yet unknown bioactive specialized metabolites, representing a huge unexploited pool of chemical diversity. Here, we describe the discovery of a novel group of catecholate-hydroxamate siderophores termed qinichelins (2–5) fromStreptomycessp. MBT76. Correlation between the metabolite levels and the protein expression profiles identified the biosynthetic gene cluster (BGC; namedqch) most likely responsible for qinichelin biosynthesis. The structure of the molecules was elucidated by bioinformatics, mass spectrometry and NMR. Synthesis of the qinichelins requires the interplay between four gene clusters, for its synthesis and for precursor supply. This biosynthetic complexity provides new insights into the challenges scientists face when applying synthetic biology approaches for natural product discovery.Pride repository reviewer account details:URL:https://www.ebi.ac.uk/pride/archive/loginProject accession: PXD006577Username: [email protected]: 3H0iM1FK

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