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Cell-free synthetic biology for natural product biosynthesis and discovery

Journal Article · · Chemical Society Reviews
DOI:https://doi.org/10.1039/d4cs01198h· OSTI ID:2532452
 [1];  [2];  [3];  [1];  [4];  [5];  [6]
  1. Vanderbilt Univ., Nashville, TN (United States)
  2. Univ. of Tennessee, Knoxville, TN (United States)
  3. University of Kent, Canterbury (United Kingdom)
  4. USDOE Joint Genome Institute (JGI), Berkeley, CA (United States)
  5. Imperial College, London (United Kingdom)
  6. Univ. of Sydney, NSW (Australia)
Natural products have applications as biopharmaceuticals, agrochemicals, and other high-value chemicals. However, there are challenges in isolating natural products from their native producers (e.g. bacteria, fungi, plants). In many cases, synthetic chemistry or heterologous expression must be used to access these important molecules. The biosynthetic machinery to generate these compounds is found within biosynthetic gene clusters, primarily consisting of the enzymes that biosynthesise a range of natural product classes (including, but not limited to ribosomal and nonribosomal peptides, polyketides, and terpenoids). Cell-free synthetic biology has emerged in recent years as a bottom-up technology applied towards both prototyping pathways and producing molecules. Recently, it has been applied to natural products, both to characterise biosynthetic pathways and produce new metabolites. This review discusses the core biochemistry of cell-free synthetic biology applied to metabolite production and critiques its advantages and disadvantages compared to whole cell and/or chemical production routes. Specifically, we review the advances in cell-free biosynthesis of ribosomal peptides, analyse the rapid prototyping of natural product biosynthetic enzymes and pathways, highlight advances in novel antimicrobial discovery, and discuss the rising use of cell-free technologies in industrial biotechnology and synthetic biology.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division (CSGB)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
2532452
Alternate ID(s):
OSTI ID: 2553917
Journal Information:
Chemical Society Reviews, Journal Name: Chemical Society Reviews Journal Issue: 9 Vol. 54; ISSN 0306-0012
Publisher:
Royal Society of ChemistryCopyright Statement
Country of Publication:
United States
Language:
English

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Accelerated chemical synthesis of peptides and small proteins journal February 1999
Ubiquitin-mediated Processing of NF-κB Transcriptional Activator Precursor p105 journal September 1995
Insights into an Unusual Nonribosomal Peptide Synthetase Biosynthesis journal October 2010
Modular optimization in metabolic engineering journal June 2021
Antimicrobial Resistance among and Therapeutic Options against Gram‐Negative Pathogens journal August 2009
Timing the start of division in E. coli : a single-cell study journal November 2008
Rifampin: Mechanisms of Action and Resistance journal July 1983
Structural insights into simocyclinone as an antibiotic, effector ligand and substrate journal November 2017
ResFinder 4.0 for predictions of phenotypes from genotypes journal August 2020
Identification of acquired antimicrobial resistance genes journal July 2012
Evolutionary Implications of Bacterial Polyketide Synthases journal June 2005
Ubiquitous mRNA decay fragments in E. coli redefine the functional transcriptome journal May 2022
antiSMASH 7.0: new and improved predictions for detection, regulation, chemical structures and visualisation journal May 2023
BioNumbers—the database of key numbers in molecular and cell biology journal October 2009
antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences journal June 2011
GenBank journal November 2012
Validation of an entirely in vitro approach for rapid prototyping of DNA regulatory elements for synthetic biology journal January 2013
BAGEL3: automated identification of genes encoding bacteriocins and (non-)bactericidal posttranslationally modified peptides journal May 2013
Synthetic circuit for exact adaptation and fold-change detection journal April 2014
Implications of macromolecular crowding and reducing conditions for in vitro ribosome construction journal April 2015
RsgA couples the maturation state of the 30S ribosomal decoding center to activation of its GTPase pocket journal May 2017
The Antibiotic Resistant Target Seeker (ARTS), an exploration engine for antibiotic cluster prioritization and novel drug target discovery journal May 2017
The effect of macromolecular crowding on single-round transcription by Escherichia coli RNA polymerase journal December 2018
Protein Synthesis in a Cell-free System from an Extreme Thermophile. journal June 1976
High-yield ‘one-pot’ biosynthesis of raspberry ketone, a high-value fine chemical journal August 2021
Development of a Pseudomonas putida cell-free protein synthesis platform for rapid screening of gene regulatory elements journal January 2018
Use of a Fractionated, Coupled Transcription-Translation System in the Study of Ribosomal Resistance Mechanisms in Antibiotic-producing Streptomyces journal May 1989
Nonribosomal biosynthesis of vancomycin-type antibiotics: a heptapeptide backbone and eight peptide synthetase modules The GenBank/EMBL/DDBJ accession number for the balhimycin biosynthetic gene sequence reported in this paper is Y16952. journal April 2002
Coarse-Grained Dynamics of Protein Synthesis in a Cell-Free System journal January 2011
Discovering new bioactive molecules from microbial sources journal March 2014
Oxidation of elongation factor G inhibits the synthesis of the D1 protein of photosystem II journal August 2007
Effects of Apramycin, a Novel Aminoglycoside Antibiotic on Bacterial Protein Synthesis journal September 1979
Cloning and expression in Escherichia coli of a hygromycin B phosphotransferase gene from Streptomyces hygroscopicus journal January 1987
Mechanism of resistance to the antibiotic trichothecin in the producing fungi journal July 1994
Effects of Escherichia coli ribosomal protein S12 mutations on cell‐free protein synthesis journal February 2004
Differential activity profiles of translation inhibitors in whole-cell and cell-free approaches journal November 2007
An inventory of the bacterial macromolecular components and their spatial organization journal March 2011
PRODUCTION OF ANTIBIOTIC SUBSTANCES BY ACTINOMYCETES* journal December 2010
Metabolic engineering of cobalamin (vitamin B12) production in Bacillus megaterium journal December 2009
Engineering Streptomyces coelicolor for heterologous expression of secondary metabolite gene clusters: Streptomyces host for heterologous expression of gene clusters journal October 2010
Permeability barriers of Gram‐negative pathogens journal June 2019
BioBits™ Explorer: A modular synthetic biology education kit journal August 2018
Biosynthesis of Complex Polyketides in a Metabolically Engineered Strain of E. coli journal March 2001
Structure and Mechanism of the Lantibiotic Cyclase Involved in Nisin Biosynthesis journal March 2006
Metagenome Mining Reveals Polytheonamides as Posttranslationally Modified Ribosomal Peptides journal September 2012
Fate of a Synthetic Polynucleotide Directing Cell-Free Protein Synthesis II. Association with Ribosomes journal November 1962
Use of a scaffold peptide in the biosynthesis of amino acid–derived natural products journal July 2019
Synthesis of proteins by automated flow chemistry journal May 2020
Evolution-inspired engineering of nonribosomal peptide synthetases journal March 2024
Evolution-guided engineering of trans -acyltransferase polyketide synthases journal March 2024
rRNA Binding Sites and the Molecular Mechanism of Action of the Tetracyclines journal August 2016
Quinolone-Mediated Bacterial Death journal August 2007
Polysome Metabolism in Escherichia coli: Amicetin, an Antibiotic That Stabilizes Polysomes journal March 1972
Molecular basis of tetracycline action: identification of analogs whose primary target is not the bacterial ribosome journal November 1991
Mechanism of action of oxazolidinones: effects of linezolid and eperezolid on translation reactions journal October 1997
Staphylococcus aureus Cell Extract Transcription-Translation Assay: Firefly Luciferase Reporter System for Evaluating Protein Translation Inhibitors journal June 2001
Structure-Guided Discovery of Novel Aminoglycoside Mimetics as Antibacterial Translation Inhibitors journal December 2005
Simocyclinone D8, an Inhibitor of DNA Gyrase with a Novel Mode of Action journal March 2005
Selman A. Waksman, Winner of the 1952 Nobel Prize for Physiology or Medicine journal January 2014
In Vivo Production of Artificial Nonribosomal Peptide Products in the Heterologous Host Escherichia coli journal June 2004
Challenges of Antibacterial Discovery journal January 2011
Protein Mobility in the Cytoplasm ofEscherichia coli journal January 1999
Modulation of Chemical Composition and Other Parameters of the Cell at Different Exponential Growth Rates journal September 2008
Draft Genome Sequence of the Fast-Growing Marine Bacterium Vibrio natriegens Strain ATCC 14048 journal August 2013
Draft Genome Sequence of the Fast-Growing Bacterium Vibrio natriegens Strain DSMZ 759 journal June 2013
Establishment of exponential growth after a nutritional shift-up in Escherichia coli B/r: accumulation of deoxyribonucleic acid, ribonucleic acid, and protein. journal January 1977
A 24-amino-acid polypeptide is essential for the biosynthesis of the coenzyme pyrrolo-quinoline-quinone journal February 1992
Tetracycline Inhibition of Cell-Free Protein Synthesis I. Binding of Tetracycline to Components of the System journal May 1966
Cryptic or Silent? The Known Unknowns, Unknown Knowns, and Unknown Unknowns of Secondary Metabolism journal October 2020
Dual-Uptake Mode of the Antibiotic Phazolicin Prevents Resistance Acquisition by Gram-Negative Bacteria journal April 2023
Full Profiling of GE81112A, an Underexplored Tetrapeptide Antibiotic with Activity against Gram-Negative Pathogens journal June 2023
Triumphs and Challenges of Natural Product Discovery in the Postgenomic Era journal August 2024
Structure and Mechanisms of Assembly-Line Polyketide Synthases journal August 2024
Drug discovery in academia journal March 2004
A Strategy for Discovery of Novel Broad-Spectrum Antibacterials Using a High-Throughput Streptococcus pneumoniae Transcription/Translation Screen journal February 2004
Bioinformatic evidence for a widely distributed, ribosomally produced electron carrier precursor, its maturation proteins, and its nicotinoprotein redox partners journal January 2011
PKMiner: a database for exploring type II polyketide synthases journal January 2012
Cell-free protein synthesis energized by slowly-metabolized maltodextrin journal January 2009
Expansion of ribosomally produced natural products: a nitrile hydratase- and Nif11-related precursor family journal May 2010
A Streptomyces coelicolor host for the heterologous expression of Type III polyketide synthase genes journal September 2015
Designed biosynthesis of 25-methyl and 25-ethyl ivermectin with enhanced insecticidal activity by domain swap of avermectin polyketide synthase journal September 2015
Refactoring of a synthetic raspberry ketone pathway with EcoFlex journal June 2021
Thermostable in vitro transcription-translation compatible with microfluidic droplets journal June 2024
Review of deep learning: concepts, CNN architectures, challenges, applications, future directions journal March 2021
Characterization of GE82832, a peptide inhibitor of translocation interacting with bacterial 30S ribosomal subunits journal May 2006
Will 10 Million People Die a Year due to Antimicrobial Resistance by 2050? journal November 2016
Valinomycin Biosynthetic Gene Cluster in Streptomyces: Conservation, Ecology and Evolution journal September 2009
Cell-Free Protein Expression under Macromolecular Crowding Conditions journal December 2011
Artificial Environments for the Co-Translational Stabilization of Cell-Free Expressed Proteins journal February 2013
Improved Cell-Free RNA and Protein Synthesis System journal September 2014
Multiplex transcriptional characterizations across diverse bacterial species using cell‐free systems journal August 2019
Protein-Protein Association in Polymer Solutions: From Dilute to Semidilute to Concentrated journal March 2007
Mechanism of Action of Streptogramins and Macrolides journal January 1996
Quinolones: Action and Resistance Updated journal August 2009
Underexplored bacteria as reservoirs of novel antimicrobial lipopeptides journal October 2022
A Brief History of the Antibiotic Era: Lessons Learned and Challenges for the Future journal January 2010
Inclusion bodies: not that bad… journal January 2014
Cell-Free Protein Synthesis From Fast-Growing Vibrio natriegens journal June 2018
Circular and Leaderless Bacteriocins: Biosynthesis, Mode of Action, Applications, and Prospects journal September 2018
Allogenous Selection of Mutational Collateral Resistance: Old Drugs Select for New Resistance Within Antibiotic Families journal October 2021
In vitro and in vivo production and split-intein mediated ligation (SIML) of circular bacteriocins journal November 2022
Cell-free protein synthesis for nonribosomal peptide synthetic biology journal February 2024
An Overview of the Medicinally Important Plant Type III PKS Derived Polyketides journal October 2021
Plant-Derived Cell-Free Biofactories for the Production of Secondary Metabolites journal January 2022
The Oligopeptide Permease Opp Mediates Illicit Transport of the Bacterial P-site Decoding Inhibitor GE81112 journal May 2016
Triaging of Culture Conditions for Enhanced Secondary Metabolite Diversity from Different Bacteria journal January 2021
Current and Emerging Methods of Antibiotic Susceptibility Testing journal May 2019
Analysis of the Innovation Trend in Cell-Free Synthetic Biology journal June 2021
A User’s Guide to Cell-Free Protein Synthesis journal March 2019
Cell-Free PURE System: Evolution and Achievements journal January 2022
TLR10 and Its Unique Anti-Inflammatory Properties and Potential Use as a Target in Therapeutics journal January 2020
Enzymatic and chemical modifications of lipopeptide antibiotic A21978C: The synthesis and evaluation of daptomycin (LY146032). journal January 1988
Rapid cell-free forward engineering of novel genetic ring oscillators journal October 2015

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