Browse
Submit Data
Databases
API
Help

Dataset Information

32 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthetic biology of antimicrobial discovery.

ABSTRACT: Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug-resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery.

SUBMITTER: Zakeri B

PROVIDER: S-EPMC3716841 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthetic biology of antimicrobial discovery.

Zakeri Bijan B Lu Timothy K TK

ACS synthetic biology 20121204 7

Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug-resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such ...[more]

PMID: 23654251

Similar Datasets

Synthetic Biology and Computer-Based Frameworks for Antimicrobial Peptide Discovery.

Project description:Antibiotic resistance is one of the greatest challenges of our time. This global health problem originated from a paucity of truly effective antibiotic classes and an increased incidence of multi-drug-resistant bacterial isolates in hospitals worldwide. Indeed, it has been recently estimated that 10 million people will die annually from drug-resistant infections by the year 2050. Therefore, the need to develop out-of-the-box strategies to combat antibiotic resistance is urgent. The biological world has provided natural templates, called antimicrobial peptides (AMPs), which exhibit multiple intrinsic medical properties including the targeting of bacteria. AMPs can be used as scaffolds and, via engineering, can be reconfigured for optimized potency and targetability toward drug-resistant pathogens. Here, we review the recent development of tools for the discovery, design, and production of AMPs and propose that the future of peptide drug discovery will involve the convergence of computational and synthetic biology principles.

| S-EPMC8734659 | biostudies-literature

Yeast synthetic biology platform generates novel chemical structures as scaffolds for drug discovery.

Project description:Synthetic biology has been heralded as a new bioengineering platform for the production of bulk and specialty chemicals, drugs, and fuels. Here, we report for the first time a series of 74 novel compounds produced using a combinatorial genetics approach in baker's yeast. Based on the concept of "coevolution" with target proteins in an intracellular primary survival assay, the identified, mostly scaffold-sized (200-350 MW) compounds, which displayed excellent biological activity, can be considered as prevalidated hits. Of the molecules found, >75% have not been described previously; 20% of the compounds exhibit novel scaffolds. Their structural and physicochemical properties comply with established rules of drug- and fragment-likeness and exhibit increased structural complexities compared to synthetically produced fragments. In summary, the synthetic biology approach described here represents a completely new, complementary strategy for hit and early lead identification that can be easily integrated into the existing drug discovery process.

| S-EPMC4046787 | biostudies-other

Modern mass spectrometry for synthetic biology and structure-based discovery of natural products.

Project description:Covering: up to 2016In this highlight, we describe the current landscape for dereplication and discovery of natural products based on the measurement of the intact mass by LC-MS. Often it is assumed that because better mass accuracy (provided by higher resolution mass spectrometers) is necessary for absolute chemical formula determination (?1 part-per-million), that it is also necessary for dereplication of natural products. However, the average ability to dereplicate tapers off at ?10 ppm, with modest improvement gained from better mass accuracy when querying focused databases of natural products. We also highlight some recent examples of how these platforms are applied to synthetic biology, and recent methods for dereplication and correlation of substructures using tandem MS data. We also offer this highlight to serve as a brief primer for those entering the field of mass spectrometry-based natural products discovery.

| S-EPMC4981503 | biostudies-literature

GPAHex-A synthetic biology platform for Type IV-V glycopeptide antibiotic production and discovery.

Project description:Glycopeptide antibiotics (GPAs) are essential for the treatment of severe infectious diseases caused by Gram-positive bacteria. The emergence and spread of GPA resistance have propelled the search for more effective GPAs. Given their structural complexity, genetic intractability, and low titer, expansion of GPA chemical diversity using synthetic or medicinal chemistry remains challenging. Here we describe a synthetic biology platform, GPAHex (GPA Heterologous expression), which exploits the genes required for the specialized GPA building blocks, regulation, antibiotic transport, and resistance for the heterologous production of GPAs. Application of the GPAHex platform results in: (1) a 19-fold increase of corbomycin titer compared to the parental strain, (2) the discovery of a teicoplanin-class GPA from an Amycolatopsis isolate, and (3) the overproduction and characterization of a cryptic nonapeptide GPA. GPAHex provides a platform for GPA production and mining of uncharacterized GPAs and provides a blueprint for chassis design for other natural product classes.

| S-EPMC7567792 | biostudies-literature

Nano-enabled synthetic biology.

Project description:Biological systems display a functional diversity, density and efficiency that make them a paradigm for synthetic systems. In natural systems, the cell is the elemental unit and efforts to emulate cells, their components, and organization have relied primarily on the use of bioorganic materials. Impressive advances have been made towards assembling simple genetic systems within cellular scale containers. These biological system assembly efforts are particularly instructive, as we gain command over the directed synthesis and assembly of synthetic nanoscale structures. Advances in nanoscale fabrication, assembly, and characterization are providing the tools and materials for characterizing and emulating the smallest scale features of biology. Further, they are revealing unique physical properties that emerge at the nanoscale. Realizing these properties in useful ways will require attention to the assembly of these nanoscale components. Attention to systems biology principles can lead to the practical development of nanoscale technologies with possible realization of synthetic systems with cell-like complexity. In turn, useful tools for interpreting biological complexity and for interfacing to biological processes will result.

| S-EPMC1948103 | biostudies-other

Putative Protein Discovery from Microalgal Genomes as a Synthetic Biology Protein Library for Heavy Metal Bio-Removal.

Project description:Synthetic biology is a principle that aims to create new biological systems with particular functions or to redesign the existing ones through bioengineering. Therefore, this principle is often utilized as a tool to put the knowledge learned to practical use in actual fields. However, there is still a great deal of information remaining to be found, and this limits the possible utilization of synthetic biology, particularly on the topic that is the focus of the present work-heavy metal bio-removal. In this work, we aim to construct a comprehensive library of putative proteins that might support heavy metal bio-removal. Hypothetical proteins were discovered from Chlorella and Scenedesmus genomes and extensively annotated. The protein structures of these putative proteins were also modeled through Alphafold2. Although a portion of this workflow has previously been demonstrated to annotate hypothetical proteins from whole genome sequences, the adaptation of such steps is yet to be done for library construction purposes. We also demonstrated further downstream steps that allow a more accurate function prediction of the hypothetical proteins by subjecting the models generated to structure-based annotation. In conclusion, a total of 72 newly discovered putative proteins were annotated with ready-to-use predicted structures available for further investigation.

| S-EPMC9405338 | biostudies-literature

Control theory meets synthetic biology.

Project description:The past several years have witnessed an increased presence of control theoretic concepts in synthetic biology. This review presents an organized summary of how these control design concepts have been applied to tackle a variety of problems faced when building synthetic biomolecular circuits in living cells. In particular, we describe success stories that demonstrate how simple or more elaborate control design methods can be used to make the behaviour of synthetic genetic circuits within a single cell or across a cell population more reliable, predictable and robust to perturbations. The description especially highlights technical challenges that uniquely arise from the need to implement control designs within a new hardware setting, along with implemented or proposed solutions. Some engineering solutions employing complex feedback control schemes are also described, which, however, still require a deeper theoretical analysis of stability, performance and robustness properties. Overall, this paper should help synthetic biologists become familiar with feedback control concepts as they can be used in their application area. At the same time, it should provide some domain knowledge to control theorists who wish to enter the rising and exciting field of synthetic biology.

| S-EPMC4971224 | biostudies-literature

Lignin valorization meets synthetic biology.

Project description:Lignin, an abundant renewable resource in nature, is a highly heterogeneous biopolymer consisting of phenylpropanoid units. It is essential for sustainable utilization of biomass to convert lignin to value-added products. However, there are technical obstacles for lignin valorization due to intrinsic heterogeneity. The emerging of synthetic biology technologies brings new opportunities for lignin breakdown and utilization. In this review, we discussed the applications of synthetic biology on lignin conversion, especially the production of value-added products, such as aromatic chemicals, ring-cleaved chemicals from lignin-derived aromatics and bio-active substances. Synthetic biology will offer new potential strategies for lignin valorization by optimizing lignin degradation enzymes, building novel artificial converting pathways, and improving the chassis of model microorganisms.

| S-EPMC6999416 | biostudies-literature

Ecological firewalls for synthetic biology.

Project description:It has been recently suggested that engineered microbial strains could be used to protect ecosystems from undesirable tipping points and biodiversity loss. A major concern in this context is the potential unintended consequences, which are usually addressed in terms of designed genetic constructs aimed at controlling overproliferation. Here we present and discuss an alternative view grounded in the nonlinear attractor dynamics of some ecological network motifs. These ecological firewalls are designed to perform novel functionalities (such as plastic removal) while containment is achieved within the resident community. That could help provide a self-regulating biocontainment. In this way, engineered organisms have a limited spread while-when required-preventing their extinction. The basic synthetic designs and their dynamical behavior are presented, each one inspired in a given ecological class of interaction. Their possible applications are discussed and the broader connection with invasion ecology outlined.

| S-EPMC9272386 | biostudies-literature

The Synthetic Nature of Biology

Project description:For centuries, biology was centred on the analysis of the microscopic and macroscopic worlds, but since the end of the 19th century it progressively adopted synthesis as a means to understand biological systems, strengthened recently by the dawn of synthetic biology. Contemporary synthetic biology is essentially composed of various “research tribes” with different methods, languages, metaphors and agendas willing to understand biological systems and—in particular—to engineer them for solving health, food, energy and environmental problems. Synthetic biology is not only an extension of traditional genetic engineering where Genetically Modified Organisms (GMOs) are produced, but it is also endowed of various elements that allow the emergence of new artificial life forms. In this chapter, a brief history of synthetic biology is presented, followed by a description of its most prominent “tribes” and a proposition for categorising the various engineering approaches currently practiced in the field. An overview of existing and nascent GMOs is also given, including some of their applications as well as biosafety and biosecurity risks. Finally, some challenges, dilemmas and paradoxes in synthetic biology beyond the bench are very briefly examined, particularly with regard to global social justice, democratization of molecular biology, environmental concerns, policy regulation, the GMO debate, media hype, public acceptance, and the issue of resurrecting extinct life.

| S-EPMC7123144 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data