scholarly journals Natural Products and Synthetic Biology: Where We Are and Where We Need To Go

mSystems ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Sylvia Kunakom ◽  
Alessandra S. Eustáquio
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Synthetic Biology ◽  
Genome Sequencing ◽  
Scientific Community ◽  
Microbial Metabolites ◽  
Bacterial Genomes ◽  
Cholesterol Lowering

ABSTRACT The biosynthetic talent of microorganisms has been harnessed for drug discovery for almost a century. Microbial metabolites not only account for the majority of antibiotics available today, but have also led to anticancer, immunosuppressant, and cholesterol-lowering drugs. Yet, inherent challenges of natural products—including inadequate supply and difficulties with structure diversification—contributed to their deprioritization as a source of pharmaceuticals. In recent years, advances in genome sequencing and synthetic biology spurred a renewed interest in natural products. Bacterial genomes encode an abundance of natural products awaiting discovery. Synthetic biology can facilitate not only discovery and improvements in supply, but also structure diversification. This perspective highlights prior accomplishments in the field of synthetic biology and natural products by the scientific community at large, including research from our laboratory. We also provide our opinion as to where we need to go to continue advancing the field.

scholarly journals Genome Mining as New Challenge in Natural Products Discovery

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 199 ◽  
Author(s):  
Luisa Albarano ◽  
Roberta Esposito ◽  
Nadia Ruocco ◽  
Maria Costantini
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Synthetic Biology ◽  
Anticancer Agents ◽  
Genome Mining ◽  
Bioactive Natural Products ◽  
Advantages And Disadvantages ◽  
A Genome ◽  
Living Organisms ◽  
Natural Drugs

Drug discovery is based on bioactivity screening of natural sources, traditionally represented by bacteria fungi and plants. Bioactive natural products and their secondary metabolites have represented the main source for new therapeutic agents, used as drug leads for new antibiotics and anticancer agents. After the discovery of the first biosynthetic genes in the last decades, the researchers had in their hands the tool to understand the biosynthetic logic and genetic basis leading to the production of these compounds. Furthermore, in the genomic era, in which the number of available genomes is increasing, genome mining joined to synthetic biology are offering a significant help in drug discovery. In the present review we discuss the importance of genome mining and synthetic biology approaches to identify new natural products, also underlining considering the possible advantages and disadvantages of this technique. Moreover, we debate the associated techniques that can be applied following to genome mining for validation of data. Finally, we review on the literature describing all novel natural drugs isolated from bacteria, fungi, and other living organisms, not only from the marine environment, by a genome-mining approach, focusing on the literature available in the last ten years.

scholarly journals NDP-rhamnose biosynthesis and rhamnosyltransferases: building diverse glycoconjugates in nature

2021 ◽  
Vol 478 (4) ◽  
pp. 685-701
Author(s):  
Ben A. Wagstaff ◽  
Azul Zorzoli ◽  
Helge C. Dorfmueller
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Scientific Community ◽  
Pathogenic Bacteria ◽  
Vaccine Development ◽  
Ongoing Study ◽  
Deoxy Sugar ◽  
Future Drug

Rhamnose is an important 6-deoxy sugar present in many natural products, glycoproteins, and structural polysaccharides. Whilst predominantly found as the l-enantiomer, instances of d-rhamnose are also found in nature, particularly in the Pseudomonads bacteria. Interestingly, rhamnose is notably absent from humans and other animals, which poses unique opportunities for drug discovery targeted towards rhamnose utilizing enzymes from pathogenic bacteria. Whilst the biosynthesis of nucleotide-activated rhamnose (NDP-rhamnose) is well studied, the study of rhamnosyltransferases that synthesize rhamnose-containing glycoconjugates is the current focus amongst the scientific community. In this review, we describe where rhamnose has been found in nature, as well as what is known about TDP-β-l-rhamnose, UDP-β-l-rhamnose, and GDP-α-d-rhamnose biosynthesis. We then focus on examples of rhamnosyltransferases that have been characterized using both in vivo and in vitro approaches from plants and bacteria, highlighting enzymes where 3D structures have been obtained. The ongoing study of rhamnose and rhamnosyltransferases, in particular in pathogenic organisms, is important to inform future drug discovery projects and vaccine development.

Natural products in complex microbiomes – Assembling multiple bacterial genomes directly through shotgun metagenomics

Planta Medica ◽  
2014 ◽  
Vol 80 (10) ◽  
Author(s):  
IJ Miller ◽  
T Weyna ◽  
C Mlot ◽  
SS Fong ◽  
K McPhail ◽  
...  
Keyword(s):  
Natural Products ◽  
Bacterial Genomes ◽  
Shotgun Metagenomics

scholarly journals Partitioning Pattern of Natural Products Based on Molecular Properties Descriptors Representing Drug-Likeness

Symmetry ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 546
Author(s):  
Miroslava Nedyalkova ◽  
Vasil Simeonov
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
De Novo ◽  
Target Prediction ◽  
Natural Compounds ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Unique Source ◽  
The Times ◽  
Partitioning Pattern

A cheminformatics procedure for a partitioning model based on 135 natural compounds including Flavonoids, Saponins, Alkaloids, Terpenes and Triterpenes with drug-like features based on a descriptors pool was developed. The knowledge about the applicability of natural products as a unique source for the development of new candidates towards deadly infectious disease is a contemporary challenge for drug discovery. We propose a partitioning scheme for unveiling drug-likeness candidates with properties that are important for a prompt and efficient drug discovery process. In the present study, the vantage point is about the matching of descriptors to build the partitioning model applied to natural compounds with diversity in structures and complexity of action towards the severe diseases, as the actual SARS-CoV-2 virus. In the times of the de novo design techniques, such tools based on a chemometric and symmetrical effect by the implied descriptors represent another noticeable sign for the power and level of the descriptors applicability in drug discovery in establishing activity and target prediction pipeline for unknown drugs properties.

Biosynthesis and synthetic biology of psychoactive natural products

2021 ◽  
Author(s):  
Cooper S. Jamieson ◽  
Joshua Misa ◽  
Yi Tang ◽  
John M. Billingsley
Keyword(s):  
Natural Products ◽  
Synthetic Biology ◽  
Biological Activities ◽  
Engineering Applications ◽  
Pathway Discovery

The biosynthetic logic employed by Nature in the construction of psychoactive natural products is reviewed, in addition to biological activities, methodologies enabling pathway discovery, and engineering applications.

A chemoinformatic analysis of atoms, scaffolds and functional groups in natural products

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Joelle Ngo Hanna ◽  
Boris D. Bekono ◽  
Luc C. O. Owono ◽  
Flavien A. A. Toze ◽  
James A. Mbah ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Physicochemical Properties ◽  
Functional Groups ◽  
Atomic Composition ◽  
Synthetic Compounds ◽  
Chemical Libraries ◽  
Synthetic Drugs ◽  
Drugs Analysis ◽  
Chemical Class

Abstract In the quest to know why natural products (NPs) have often been considered as privileged scaffolds for drug discovery purposes, many investigations into the differences between NPs and synthetic compounds have been carried out. Several attempts to answer this question have led to the investigation of the atomic composition, scaffolds and functional groups (FGs) of NPs, in comparison with synthetic drugs analysis. This chapter briefly describes an atomic enumeration method for chemical libraries that has been applied for the analysis of NP libraries, followed by a description of the main differences between NPs of marine and terrestrial origin in terms of their general physicochemical properties, most common scaffolds and “drug-likeness” properties. The last parts of the work describe an analysis of scaffolds and FGs common in NP libraries, focusing on huge NP databases, e.g. those in the Dictionary of Natural Products (DNP), NPs from cyanobacteria and the largest chemical class of NP – terpenoids.

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