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 titer was further achieved by (1) protein engineering of rate-limiting tryptophan hydroxylase to improve 5-hydroxytryptophan biosynthesis and (2) chromosomal integration of aromatic-amino-acid decarboxylase to limit byproduct formation and to minimize gene toxicity to the host cell. Fermentation optimization improved melatonin titer by an additional 2-fold. Deletion of yddG, a tryptophan exporter, exhibited an additive beneficial effect. The final engineered strain produced ∼2.0 g/L of melatonin with tryptophan supplemented externally and ∼1.0 g/L with glucose as the sole carbon source for tryptophan supply. This study lays the foundation for further developing a commercial melatonin-producing E. coli strain.
journal_name
ACS Synth Bioljournal_title
ACS synthetic biologyauthors
Luo H,Schneider K,Christensen U,Lei Y,Herrgard M,Palsson BØdoi
10.1021/acssynbio.0c00065subject
Has Abstractpub_date
2020-06-19 00:00:00pages
1240-1245issue
6issn
2161-5063journal_volume
9pub_type
杂志文章abstract：:Sporulated cells have potential as time-delayed expression chassis of proteins for applications such as "on-demand" biologics production, whole cell biosensors, or oral vaccines. However, the desired attributes of high expression rates and low product variances are difficult to maintain from germinated spores. In this...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00163
更新日期：2019-10-18 00:00:00
abstract：:Feedback control allows cells to dynamically sense and respond to environmental changes. However, synthetic controller designs can be challenging because of implementation issues, such as determining optimal expression levels for circuit components within a feedback loop. Here, we addressed this by coupling rational d...
journal_title：ACS synthetic biology
pub_type： 信件
doi：10.1021/acssynbio.7b00260
更新日期：2018-01-19 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：:Although recent advances in synthetic biology allow us to produce biological designs more efficiently than ever, our ability to predict the end result of these designs is still nascent. Predictive models require large amounts of high-quality data to be parametrized and tested, which are not generally available. Here, ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.7b00204
更新日期：2017-12-15 00:00:00
abstract：:While inducing agents are often used to redirect resources from growth and proliferation toward product outputs, they can be prohibitively expensive on the industrial scale. Previously, we developed an autonomously guided protein production system based on the rewiring of E. coli's native quorum sensing (QS) signal tr...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.5b00261
更新日期：2016-09-16 00:00:00
abstract：:Synthetic biology is today harnessing the design of novel and greener biosynthesis routes for the production of added-value chemicals and natural products. The design of novel pathways often requires a detailed selection of enzyme sequences to import into the chassis at each of the reaction steps. To address such desi...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.5b00294
更新日期：2016-06-17 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
abstract：:Transcription activator-like effectors (TALEs) are proteins secreted by Xanthomonas bacteria to aid the infection of plant species. TALEs assist infections by binding to specific DNA sequences and activating the expression of host genes. Recent results show that TALE proteins consist of a central repeat domain, which ...
journal_title：ACS synthetic biology
pub_type： 杂志文章,评审
doi：10.1021/sb400137b
更新日期：2014-10-17 00:00:00
abstract：:The methods to execute biological experiments are evolving. Affordable fluid handling robots and on-demand biology enterprises are making automating entire experiments a reality. Automation offers the benefit of high-throughput experimentation, rapid prototyping, and improved reproducibility of results. However, learn...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.6b00304
更新日期：2017-07-21 00:00:00
abstract：:This paper describes SBOLExplorer, a system that is used to provide intuitive searching within the SynBioHub genetic design repository. SynBioHub stores genetic constructs encoded in the SBOL data format. These constructs can represent genetic parts, circuits, and sequences. These constructs are often numerous, exist ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00089
更新日期：2019-10-18 00:00:00
abstract：:To spatially control biochemical functions at specific sites within a genome, we have engineered a synthetic switch that activates when bound to its DNA target site. The system uses two CRISPR-Cas complexes to colocalize components of a de novo-designed protein switch (Co-LOCKR) to adjacent sites in the genome. Coloca...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.0c00012
更新日期：2020-09-18 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：:Dramatic improvements to computational, robotic, and biological tools have enabled genetic engineers to conduct increasingly sophisticated experiments. Further development of biological tools offers a route to bypass complex or expensive mechanical operations, thereby reducing the time and cost of highly parallelized ...
journal_title：ACS synthetic biology
pub_type： 信件
doi：10.1021/sb300054p
更新日期：2012-12-21 00:00:00
abstract：:Synthetic biology holds promise to engineer systems to treat diseases. One critical, yet underexplored, facet of designing such systems is the interplay between the system and the pathogen. Understanding this interplay may be critical to increasing efficacy and overcoming resistance against the system. Using the princ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.5b00192
更新日期：2016-03-18 00:00:00
abstract：:Modern bioprocessing depends on superior cellular traits, many stemming from unknown genes and gene interactions. Tolerance to toxic chemicals is such an industrially important complex trait, which frequently limits the economic feasibility of producing commodity chemicals and biofuels. Chemical tolerance encompasses ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb400156v
更新日期：2014-07-18 00:00:00
abstract：:The microbial ability to resist stressful environmental conditions and chemical inhibitors is of great industrial and medical interest. Much of the data related to mutation-based stress resistance, however, is scattered through the academic literature, making it difficult to apply systematic analyses to this wealth of...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.6b00150
更新日期：2016-12-16 00:00:00
abstract：:As engineering foundations such as standards and abstraction begin to mature within synthetic biology, it is vital that genetic design automation (GDA) tools be developed to enable synthetic biologists to automatically select standardized DNA components from a library to meet the behavioral specification for a genetic...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb400135t
更新日期：2014-08-15 00:00:00
abstract：:A bacterial flavin transferase (ApbE) was recently employed for flavin mononucleotide (FMN) modification on the Na+-translocating NADH:quinone oxidoreductase C (NqrC) protein in the pathogenic Gram-negative bacterium Vibrio cholerae. We employed this unique post-translational modification in mammalian cells and found ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.6b00284
更新日期：2017-04-21 00:00:00
abstract：:We study translation repression in bacteria by engineering a regulatory circuit that functions as a binding assay for RNA binding proteins (RBP) in vivo. We do so by inducing expression of a fluorescent protein-RBP chimera, together with encoding its binding site at various positions within the ribosomal initiation re...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.8b00378
更新日期：2018-12-21 00:00:00
abstract：:Recent advances in the design and construction of synthetic multicelled systems in E. coli and S. cerevisiae suggest that it may be possible to implement sophisticated distributed algorithms with these relatively simple organisms. However, existing design frameworks for synthetic biology do not account for the unique ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb300034m
更新日期：2012-08-17 00:00:00
abstract：:Bacterial biofilms are three-dimensional networks of cells entangled in a self-generated extracellular polymeric matrix composed of proteins, lipids, polysaccharides, and nucleic acids. Biofilms can establish themselves on virtually any accessible surface and lead to varying impacts ranging from infectious diseases to...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.9b00192
更新日期：2019-07-19 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：: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：:Simple computation can be performed using the interactions between single-stranded molecules of DNA. These interactions are typically toehold-mediated strand displacement reactions in a well-mixed solution. We demonstrate that a DNA circuit with tethered reactants is a distributed system and show how it can be describ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.5b00275
更新日期：2016-08-19 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：:The cell contents are encapsulated within a compartment, the volume of which is a fundamental physical parameter that may affect intracompartmental reactions. However, there have been few studies to elucidate whether and how volume changes alone can affect the reaction kinetics. It is difficult to address these questi...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/sb300041z
更新日期：2012-09-21 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：: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：:Synthetic biology and metabolic engineering offer potentially green and attractive routes to the production of high value compounds. The provision of high-quality parts and pathways is crucial in enabling the biosynthesis of chemicals using synthetic biology. While a number of regulatory parts that provide control at ...
journal_title：ACS synthetic biology
pub_type： 杂志文章
doi：10.1021/acssynbio.0c00375
更新日期：2020-10-16 00:00:00
abstract：:The Sc2.0 project is perhaps the largest synthetic biology project in the public domain, and ultimately aims to construct a new version of the humble brewer's yeast, Saccharomyces cerevisiae. Each year, the Sc2.0 consortium gather to discuss progress in this ambitious project and highlight new developments at the fore...
journal_title：ACS synthetic biology
pub_type： 杂志文章,评审
doi：10.1021/acssynbio.6b00227
更新日期：2016-09-16 00:00:00
