Abstract：
:Novel approaches are needed to combat antibiotic resistance. Here, we describe a computational-experimental framework for the discovery of novel cryptic antimicrobial peptides (AMPs). The computational platform, based on previously validated antimicrobial scoring functions, indicated the activation peptide of pepsin A, the main human stomach protease, and its N- and C-terminal halves as antimicrobial peptides. The three peptides from pepsinogen A3 isoform were prepared in a recombinant form using a fusion carrier specifically developed to express toxic peptides in Escherichia coli. Recombinant pepsinogen A3-derived peptides proved to be wide-spectrum antimicrobial agents with MIC values in the range 1.56-50 μM (1.56-12.5 μM for the whole activation peptide). Moreover, the activation peptide was bactericidal at pH 3.5 for relevant foodborne pathogens, suggesting that this new class of previously unexplored AMPs may contribute to microbial surveillance within the human stomach. The peptides showed no toxicity toward human cells and exhibited anti-infective activity in vivo, reducing by up to 4 orders of magnitude the bacterial load in a mouse skin infection model. These peptides thus represent a promising new class of antibiotics. We envision that computationally guided data mining approaches such as the one described here will lead to the discovery of antibiotics from previously unexplored sources.
journal_name
ACS Synth Bioljournal_title
ACS synthetic biologyauthors
Pane K,Cafaro V,Avitabile A,Torres MT,Vollaro A,De Gregorio E,Catania MR,Di Maro A,Bosso A,Gallo G,Zanfardino A,Varcamonti M,Pizzo E,Di Donato A,Lu TK,de la Fuente-Nunez C,Notomista Edoi
10.1021/acssynbio.8b00084subject
Has Abstractpub_date
2018-09-21 00:00:00pages
2105-2115issue
9issn
2161-5063journal_volume
7pub_type
杂志文章abstract：:Improved plants are necessary to meet human needs. Agrobacterium-mediated transformation is the most common method used to rewire plant capabilities. For plant gene delivery, DNA constructs are assembled into binary T-DNA vectors that rely on broad host range origins for bacterial replication. Here we present pLX vect...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.6b00354
更新日期：2017-10-20 00:00:00
abstract：:One limitation of gene-directed enzyme prodrug therapy (GDEPT) is the difficulty in selectively and efficiently transducing cancer cells with the gene encoding a prodrug-converting enzyme. To circumvent this issue, we sought to move the selectivity from the gene delivery level to the protein level. We developed fusion...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00036
更新日期：2019-05-17 00:00:00
abstract：:Microbial electrosynthesis is an emerging technology with the potential to simultaneously store renewably generated energy, fix carbon dioxide, and produce high-value organic compounds. However, limited understanding of the route of electrons into the cell remains an obstacle to developing a robust microbial electrosy...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.8b00498
更新日期：2019-07-19 00:00:00
abstract：:Cellobiose phosphorylase (CBP) cleaves cellobiose-abundant in plant biomass-to glucose and glucose 1-phosphate. However, the pentose sugar xylose, also abundant in plant biomass, acts as a mixed-inhibitor and a substrate for the reverse reaction, limiting the industrial potential of CBP. Preventing xylose, which lacks...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.6b00211
更新日期：2017-02-17 00:00:00
abstract：:Allosteric proteins, which can sense different signals, are interesting biological parts for synthetic biology. In particular, the design of an artificial allosteric enzyme to sense an unnatural signal is both challenging and highly desired, for example, for a precise and dynamical control of fluxes of growth-essentia...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb400133g
更新日期：2015-02-20 00:00:00
abstract：:A significant bottleneck in synthetic biology involves screening large genetically encoded libraries for desirable phenotypes such as chemical production. However, transcription factor-based biosensors can be leveraged to screen thousands of genetic designs for optimal chemical production in engineered microbes. In th...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00255
更新日期：2019-10-18 00:00:00
abstract：:In many biotechnological applications, it is useful for gene expression to be regulated by multiple signals, as this allows the programming of complex behavior. Here we implement, in Escherichia coli, a system that compares the concentration of two signal molecules, and tunes GFP expression proportionally to their rel...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.7b00109
更新日期：2017-10-20 00:00:00
abstract：:A defining goal of synthetic biology is to develop biomaterials with superior performance and versatility. Here we introduce a purely genetically encoded and self-assembling biopolymer based on the SpyTag-SpyCatcher chemistry. We show the application of this polymer for highly efficient uranyl binding and extraction f...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.8b00223
更新日期：2018-10-19 00:00:00
abstract：:Phages are biological entities found in every ecosystem. Although much has been learned about them in past decades, significant knowledge gaps remain. Manipulating virulent phage genomes is challenging. To date, no efficient gene-editing tools exist for engineering virulent lactococcal phages. Lactococcus lactis is a ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.6b00388
更新日期：2017-07-21 00:00:00
abstract：:Synonymous mutation of the N-terminal coding sequence (NCS) has been used to regulate gene expression. We here developed a statistical model to predict the effect of the NCSs on protein expression in Bacillus subtilis WB600. First, a synonymous mutation was performed within the first 10 residues of a superfolder green...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.0c00309
更新日期：2021-01-19 00:00:00
abstract：:Synthetic biology relies on the manufacture of large and complex DNA constructs from libraries of genetic parts. Golden Gate and other Type IIS restriction enzyme-dependent DNA assembly methods enable rapid construction of genes and operons through one-pot, multifragment assembly, with the ordering of parts determined...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.8b00333
更新日期：2018-11-16 00:00:00
abstract：:Engineered bacteria promise to revolutionize diagnostics and therapeutics, yet many applications are precluded by the limited number of detectable signals. Here we present a general framework to engineer synthetic receptors enabling bacterial cells to respond to novel ligands. These receptors are activated via ligand-...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.7b00266
更新日期：2018-01-19 00:00:00
abstract：:Cell-free gene expression systems are emerging as an important platform for a diverse range of synthetic biology and biotechnology applications, including production of robust field-ready biosensors. Here, we combine programmed cellular autolysis with a freeze-thaw or freeze-dry cycle to create a practical, reproducib...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.7b00253
更新日期：2017-12-15 00:00:00
abstract：:Directed evolution requires the creation of genetic diversity and subsequent screening or selection for improved variants. For DNA mutagenesis, conventional site-directed methods implicitly utilize the Boolean AND operator (creating all mutations simultaneously), producing a combinatorial explosion in the number of ge...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00063
更新日期：2019-06-21 00:00:00
abstract：:A major force shaping form and patterns in biology is based in the presence of amplification mechanisms able to generate ordered, large-scale spatial structures out of local interactions and random initial conditions. Turing patterns are one of the best known candidates for such ordering dynamics, and their existence ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.5b00254
更新日期：2016-07-15 00:00:00
abstract：:The deeply red-colored natural compound prodigiosin is a representative of the prodiginine alkaloid family, which possesses bioactivities as antimicrobial, antitumor, and antimalarial agents. Various bacteria including the opportunistic human pathogen Serratia marcescens and different members of the Streptomycetaceae ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.7b00099
更新日期：2017-09-15 00:00:00
abstract：:In this work we report synthetic adhesins (SAs) enabling the rational design of the adhesion properties of E. coli. SAs have a modular structure comprising a stable β-domain for outer membrane anchoring and surface-exposed immunoglobulin domains with high affinity and specificity that can be selected from large repert...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb500252a
更新日期：2015-04-17 00:00:00
abstract：:Design and implementation of synthetic biological circuits highly depends on well-characterized, robust promoters with predictable input-output responses. While great progress has been made with heterotrophic model organisms such as Escherichia coli, the available variety of tunable promoter parts for phototrophic cya...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00505
更新日期：2020-04-17 00:00:00
abstract：:Agricultural soils are often cocontaminated with multiple pesticides. Unfortunately, microorganisms isolated from natural environments do not possess the ability to simultaneously degrade different classes of pesticides. Currently, we can use the approaches of synthetic biology to create a strain endowed with various ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.6b00025
更新日期：2016-05-20 00:00:00
abstract：:Transform-MinER (Transforming Molecules in Enzyme Reactions) is a web application facilitating the exploration of chemical biosynthetic space, guiding the user toward promising start points for enzyme design projects or directed evolution experiments. Two types of search are possible: Molecule Search allows a user to ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00105
更新日期：2019-11-15 00:00:00
abstract：:To program cells in a dynamic manner, synthetic biologists require precise control over the threshold levels and timing of gene expression. However, in practice, modulating gene expression is widely carried out using prototypical ligand-inducible promoters, which have limited tunability and spatiotemporal resolution. ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.8b00280
更新日期：2018-11-16 00:00:00
abstract：:An RNA-dependent RNA polymerase ribozyme that was highly optimized through in vitro evolution for the ability to copy a broad range of template sequences exhibits promiscuity toward other nucleic acids and nucleic acid analogues, including DNA, threose nucleic acid (TNA), and arabinose nucleic acid (ANA). By operating...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00044
更新日期：2019-05-17 00:00:00
abstract：:While engineered chimeric antigen receptor (CAR) T cells have shown promise in detecting and eradicating cancer cells within patients, it remains difficult to identify a set of truly cancer-specific CAR-targeting cell surface antigens to prevent potentially fatal on-target off-tumor toxicity against other healthy tiss...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00175
更新日期：2019-10-18 00:00:00
abstract：:Melatonin is a commercially attractive tryptophan-derived hormone. Here we describe a bioprocess for the production of melatonin using Escherichia coli to high titers. The first engineered strain produced 0.13 g/L of melatonin from tryptophan under fed-batch fermentation conditions. A 4-fold improvement on melatonin t...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.0c00065
更新日期：2020-06-19 00:00:00
abstract：:Light-switchable proteins enable unparalleled control of molecular biological processes in live organisms. Previously, we have engineered red/far-red and green/red photoreversible two-component signal transduction systems (TCSs) with transcriptional outputs in E. coli and used them to characterize and control syntheti...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb500273n
更新日期：2014-11-21 00:00:00
abstract：:RNA parts often serve as critical components in genetic engineering. Here we report a design of translational activators which is composed of an RNA endoribonuclease (Csy4) and two exchangeable RNA modules. Csy4, a member of Cas endoribonuclease, cleaves at a specific recognition site; this cleavage releases a cis-rep...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.5b00130
更新日期：2016-01-15 00:00:00
abstract：:Noncanonical amino acids form a highly diverse pool of building blocks that can render unique physicochemical properties to peptides and proteins. Here, four methionine analogues with unsaturated and varying side chain lengths were successfully incorporated at four different positions in nisin in Lactococcus lactis th...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.0c00308
更新日期：2020-09-18 00:00:00
abstract：:In order to match our ability to conceive of and construct cells with enhanced function, we must concomitantly develop facile, real-time methods for elucidating performance. With these, new designs can be tested in silico and steps in construction incrementally validated. Electrochemical monitoring offers the above ad...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.5b00073
更新日期：2016-01-15 00:00:00
abstract：:Trihydroxycinnamoyl spermidines (THCSpd) are plant specialized metabolites with promising pharmacological activities as antifungals, antibacterial, antiviral, and antidepressant drugs. However, their characterization and potential pharmaceutical exploitation are greatly impaired by the sourcing of these compounds, res...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.0c00391
更新日期：2021-01-15 00:00:00
abstract：:Owl ( www.owlcad.org ) is a biodesign automation tool that generates electronic datasheets for synthetic biological parts using common formatting. Data can be retrieved automatically from existing repositories and modified in the Owl user interface (UI). Owl uses the data to generate an HTML page with standard typeset...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb500053j
更新日期：2014-12-19 00:00:00
