Heterologous expression of a single fungal HR-PKS leads to the formation of diverse 2-alkenyl-tetrahydropyrans in model fungi

2021 ◽  
Author(s):  
Hai-Ning Lyu ◽  
Jinyu Zhang ◽  
Shuang Zhou ◽  
Hongwei Liu ◽  
Wenying Zhuang ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Development ◽  
Heterologous Expression ◽  
Structural Instability ◽  
Antifungal Activities ◽  
Rare Class

2-Alkenyl-tetrahydropyrans belong to a rare class of natural products that exhibit broad antifungal activities. The structural instability and rareness in nature restrained their discovery and drug development. In this study,...

scholarly journals Microbial biotransformation as a tool for drug development based on natural products from mevalonic acid pathway: A review

2015 ◽  
Vol 6 (1) ◽  
pp. 17-33 ◽  
Author(s):  
Mohamed-Elamir F. Hegazy ◽  
Tarik A. Mohamed ◽  
Abdelsamed I. ElShamy ◽  
Abou-El-Hamd H. Mohamed ◽  
Usama A. Mahalel ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Development ◽  
Mevalonic Acid ◽  
Mevalonic Acid Pathway ◽  
Acid Pathway

scholarly journals Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

2014 ◽  
Vol 10 ◽  
pp. 1228-1232 ◽  
Author(s):  
Jens Schmidt ◽  
Zeinab Khalil ◽  
Robert J Capon ◽  
Christian B W Stark
Keyword(s):  
Antibacterial Activity ◽  
Natural Products ◽  
Total Synthesis ◽  
Asymmetric Synthesis ◽  
Natural Product ◽  
Joint Effort ◽  
Natural Product Biosynthesis ◽  
New Members ◽  
Degree Of Oxidation ◽  
Rare Class

The heronapyrroles A–C have first been isolated from a marine-derived Streptomyces sp. (CMB-0423) in 2010. Structurally, these natural products feature an unusual nitropyrrole system to which a partially oxidized farnesyl chain is attached. The varying degree of oxidation of the sesquiterpenyl subunit in heronapyrroles A–C provoked the hypothesis that there might exist other hitherto unidentified metabolites. On biosynthetic grounds a mono-tetrahydrofuran-diol named heronapyrrole D appeared a possible candidate. We here describe a short asymmetric synthesis of heronapyrrole D, its detection in cultivations of CMB-0423 and finally the evaluation of its antibacterial activity. We thus demonstrate that biosynthetic considerations and the joint effort of synthetic and natural product chemists can result in the identification of new members of a rare class of natural products.

scholarly journals Discovery and Biosynthesis of Natural Products from New Zealand Soil Metagenome Libraries

2021 ◽  
Author(s):  
◽  
Luke Stevenson
Keyword(s):  
Natural Products ◽  
New Zealand ◽  
Heterologous Expression ◽  
Gene Clusters ◽  
Bioinformatic Analysis ◽  
Coli Strain ◽  
Functional Screening ◽  
Functional Difference ◽  
Biosynthetic Pathways ◽  
New Members

<p>Antibiotic discovery rates dramatically declined following the “golden age” of the 1940’s to the 1960’s. The platforms that underpinned that age of discovery rested upon laboratory cultivation of a small clade of bacteria, the actinomycetes, primarily isolated from soil environments. Fermentation extracts of these isolated bacteria have provided the majority of antibiotics and anticancer small molecules still used today. By applying modern genetic analysis techniques to these same environmental sources that have previously yielded such success, we can uncover new biosynthetic pathways, and bioactive compounds. The work described in this thesis investigated New Zealand soil metagenomes for this purpose.  Four large metagenome libraries were constructed from the microbiomes of diverse soil environments. These were then interrogated by a functional screening approach in a knockout Escherichia coli strain, to recover a large collection of the biosynthetic gene clusters responsible for bacterial secondary metabolite production. Using different modes of bioinformatic analysis, these gene clusters were demonstrated to have both phylogenetic divergence, and functional difference from bacterial biosynthesis pathways previously discovered from culture based studies.  Two additional biosynthetic pathways were recovered from one of these metagenome libraries, and in each case found to have novel genetic features. These gene clusters were further studied by heterologous expression within Streptomyces albus production hosts. One of these gene clusters produced small aromatic polyketide compounds, the structure of one of which was solved by chemical analytic techniques, and found to be a new chemical entity.  The second gene cluster was demonstrated to have similarity to known aureolic acid biosynthesis gene clusters – a class of potent anticancer natural products. Heterologous expression resulted in the production of many metabolites, two of which were characterised and found to be new members of this chemical class.  The research in this thesis both validates the use of metagenomic analysis for future natural product discovery efforts, and adds to a growing body of evidence that understudied clades of bacteria have an untapped biosynthetic potential that can be accessed by metagenomic methods.</p>

Potential Phytochemical Nanoemulsions in the Treatment of Oral Cancer and Oral Health

2022 ◽  
pp. 330-353
Author(s):  
Dharmeswar Barhoi ◽  
Sweety Nath Barbhuiya ◽  
Sarbani Giri
Keyword(s):  
Natural Products ◽  
Radiation Therapy ◽  
Oral Health ◽  
Side Effects ◽  
Oral Cancer ◽  
Medicinal Plants ◽  
Drug Development ◽  
Health Management ◽  
Free Form ◽  
New Drug Development

Oral cancer is one of the most common types of cancer, and lifestyle factors like extensive consumption of tobacco, betel quid, and alcohol are the major etiological factors of oral cancer. Treatment of oral cancer includes surgery, radiation therapy, and chemotherapy, but this treatment possesses lots of side effects. Therefore, scientists and medical experts are utilizing natural products and medicinal plants for new drug development. Natural products and phytochemicals showed better efficacy with less toxicity. However, most of the phytochemicals showed poor permeability and less bioavailability. To combat this problem, scientists developed nanosized nanoemulsions of phytochemicals to treat various ailments. Nanoemulsions of phytochemicals exhibited better efficacy than their free form due to increased permeability and bioavailability. Numerous phytopharmaceuticals have been formulated for nanoemulsions to date and tested for their anticancer potential against various cancers, including oral cancer and oral health management.

scholarly journals Expanding the Natural Products Heterologous Expression Repertoire in the Model Cyanobacterium Anabaena sp. Strain PCC 7120: Production of Pendolmycin and Teleocidin B-4

2019 ◽  
Vol 9 (1) ◽  
pp. 63-75 ◽  
Author(s):  
Patrick Videau ◽  
Kaitlyn N. Wells ◽  
Arun J. Singh ◽  
Jessie Eiting ◽  
Philip J. Proteau ◽  
...  
Keyword(s):  
Natural Products ◽  
Heterologous Expression ◽  
Cyanobacterium Anabaena ◽  
Anabaena Sp ◽  
Pcc 7120

scholarly journals Heterologous Expression of a Cryptic Gene Cluster from Streptomyces leeuwenhoekii C34T Yields a Novel Lasso Peptide, Leepeptin

2019 ◽  
Vol 85 (23) ◽  
Author(s):  
Juan Pablo Gomez-Escribano ◽  
Jean Franco Castro ◽  
Valeria Razmilic ◽  
Scott A. Jarmusch ◽  
Gerhard Saalbach ◽  
...  
Keyword(s):  
Natural Products ◽  
Heterologous Expression ◽  
Streptomyces Coelicolor ◽  
Gene Clusters ◽  
Bioinformatic Analysis ◽  
Growth Media ◽  
Content Type ◽  
Lasso Peptide ◽  
Lasso Peptides ◽  
New Family

ABSTRACT Analysis of the genome sequence of Streptomyces leeuwenhoekii C34T identified biosynthetic gene clusters (BGCs) for three different lasso peptides (Lp1, Lp2, and Lp3) which were not known to be made by the strain. Lasso peptides represent relatively new members of the RiPP (ribosomally synthesized and posttranslationally modified peptides) family of natural products and have not been extensively studied. Lp3, whose production could be detected in culture supernatants from S. leeuwenhoekii C34T and after heterologous expression of its BGC in Streptomyces coelicolor, is identical to the previously characterized chaxapeptin. Lp1, whose production could not be detected or achieved heterologously, appears to be identical to a recently identified member of the citrulassin family of lasso peptides. Since production of Lp2 by S. leeuwenhoekii C34T was not observed, its BGC was also expressed in S. coelicolor. The lasso peptide was isolated and its structure confirmed by mass spectrometry and nuclear magnetic resonance analyses, revealing a novel structure that appears to represent a new family of lasso peptides. IMPORTANCE Recent developments in genome sequencing combined with bioinformatic analysis have revealed that actinomycetes contain a plethora of unexpected BGCs and thus have the potential to produce many more natural products than previously thought. This reflects the inability to detect the production of these compounds under laboratory conditions, perhaps through the use of inappropriate growth media or the absence of the environmental cues required to elicit expression of the corresponding BGCs. One approach to overcoming this problem is to circumvent the regulatory mechanisms that control expression of the BGC in its natural host by deploying heterologous expression. The generally compact nature of lasso peptide BGCs makes them particularly amenable to this approach, and, in the example given here, analysis revealed a new member of the lasso peptide family of RiPPs. This approach should be readily applicable to other cryptic lasso peptide gene clusters and would also facilitate the design and production of nonnatural variants by changing the sequence encoding the core peptide, as has been achieved with other classes of RiPPs.

scholarly journals Natural products from filamentous fungi and production by heterologous expression

2016 ◽  
Vol 101 (2) ◽  
pp. 493-500 ◽  
Author(s):  
Fabrizio Alberti ◽  
Gary D. Foster ◽  
Andy M. Bailey
Keyword(s):  
Natural Products ◽  
Heterologous Expression ◽  
Filamentous Fungi

Cheminformatics techniques in antimalarial drug discovery and development from natural products 1: basic concepts

2019 ◽  
Vol 4 (7) ◽  
Author(s):  
Samuel Egieyeh ◽  
Sarel F. Malan ◽  
Alan Christoffels
Keyword(s):  
Natural Products ◽  
Drug Development ◽  
Antimalarial Drug ◽  
Drug Discovery And Development ◽  
Drug Candidates ◽  
Structure Activity ◽  
Preclinical And Clinical Studies ◽  
Research Cost

Abstract A large number of natural products, especially those used in ethnomedicine of malaria, have shown varying in vitro antiplasmodial activities. Facilitating antimalarial drug development from this wealth of natural products is an imperative and laudable mission to pursue. However, limited manpower, high research cost coupled with high failure rate during preclinical and clinical studies might militate against the pursuit of this mission. These limitations may be overcome with cheminformatic techniques. Cheminformatics involves the organization, integration, curation, standardization, simulation, mining and transformation of pharmacology data (compounds and bioactivity) into knowledge that can drive rational and viable drug development decisions. This chapter will review the application of cheminformatics techniques (including molecular diversity analysis, quantitative-structure activity/property relationships and Machine learning) to natural products with in vitro and in vivo antiplasmodial activities in order to facilitate their development into antimalarial drug candidates and design of new potential antimalarial compounds.

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