From Context to Code: Rational De Novo DNA Design and Predicting Cross-Species DNA Functionality Using Deep Learning Transformer Models DOI Creative Commons
Gurvinder Singh Dahiya,

Thea Isabel Bakken,

Maxime Fages‐Lartaud

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 15, 2023

ABSTRACT Synthetic biology currently operates under a framework dominated by trial-and-error approaches, which hinders the effective engineering of organisms and expansion large-scale biomanufacturing. Motivated success computational designs in areas like architecture aeronautics, we aspire to transition more efficient predictive methodology synthetic biology. In this study, report DNA Design Platform that relies on power Transformer-based deep learning architectures. The platform transforms conventional paradigms enabling context-sensitive host-specific 5′ regulatory elements—promoters untranslated regions (UTRs) along with an array codon-optimised coding sequence (CDS) variants. This allows us generate sequences CDSs, achieving unparalleled level specificity adaptability different target hosts. With context-aware design, significantly broaden range possible gene expression profiles phenotypic outcomes, substantially reducing need for laborious high-throughput screening efforts. Our context-aware, AI-driven design strategy marks significant advancement biology, offering scalable refined approach optimisation across diverse summary, study represents substantial leap forward field, utilising models transform build, test, learn-cycle into framework.

Language: Английский

Pseudomonas putida as a synthetic biology chassis and a metabolic engineering platform DOI Creative Commons
Esteban Martínez‐García, Vı́ctor de Lorenzo

Current Opinion in Biotechnology, Journal Year: 2023, Volume and Issue: 85, P. 103025 - 103025

Published: Dec. 7, 2023

The soil bacterium Pseudomonas putida, especially the KT2440 strain, is increasingly being utilized as a host for biotransformations of both industrial and environmental interest. foundations such performance include its robust redox metabolism, ability to tolerate wide range physicochemical stresses, rapid growth, versatile nonpathogenic nature, availability molecular tools advanced genetic programming. These attributes have been leveraged hosting engineered pathways production valuable chemicals or degradation/valorization pollutants. This has in turn pushed boundaries conventional enzymology toward previously unexplored reactions nature. Furthermore, modifications physical properties cells made enhance their catalytic performance. advancements establish P. putida bona fide chassis synthetic biology, on par with more traditional metabolic engineering platforms.

Language: Английский

Citations

34
Reduction-to-synthesis: the dominant approach to genome-scale synthetic biology DOI Creative Commons
Kangsan Kim, Donghui Choe, Suhyung Cho

et al.

Trends in biotechnology, Journal Year: 2024, Volume and Issue: 42(8), P. 1048 - 1063

Published: Feb. 28, 2024

Advances in systems and synthetic biology have propelled the construction of reduced bacterial genomes. Genome reduction was initially focused on exploring properties minimal genomes, but more recently it has been deployed as an engineering strategy to enhance strain performance. This review provides latest updates focusing dual-track approaches top-down bottom-up synthesis for their construction. Using cases from studies that are based established industrial workhorse strains, we discuss a series phenotypes candidates biotechnological applications. Finally, address possible uses genomes applications needed future research directions may ultimately lead total rationally designed

Language: Английский

Citations

11
AutoBioTech─A Versatile Biofoundry for Automated Strain Engineering DOI Creative Commons
Tobias Michael Rosch, Julia Tenhaef,

Thomas Stoltmann

et al.

ACS Synthetic Biology, Journal Year: 2024, Volume and Issue: 13(7), P. 2227 - 2237

Published: July 8, 2024

The inevitable transition from petrochemical production processes to renewable alternatives has sparked the emergence of biofoundries in recent years. Manual engineering microbes will not be sufficient meet ever-increasing demand for novel producer strains. Here we describe AutoBioTech platform, a fully automated laboratory system with 14 devices perform operations strain construction without human interaction. Using modular workflows, this platform enables transformations Escherichia coli plasmids assembled via cloning. A CRISPR/Cas9 toolbox compatible existing cloning frameworks allows and flexible genome editing E. coli. In addition, workflows have been established transformation Gram-positive model organism Corynebacterium glutamicum by conjugation electroporation, latter proving more robust technique. Overall, excels at versatility due modularity seamless transitions between modules. This accelerate Gram-negative bacteria.

Language: Английский

Citations

8
Engineering oleaginous red yeasts as versatile chassis for the production of olechemicals and valuable compounds: Current advances and perspectives DOI
Guiping Gong, Bo Wu,

Linpei Liu

et al.

Biotechnology Advances, Journal Year: 2024, Volume and Issue: 76, P. 108432 - 108432

Published: Aug. 18, 2024

Language: Английский

Citations

8
Physiology-informed use of Cupriavidus necator in biomanufacturing: a review of advances and challenges DOI Creative Commons

M. K. Weldon,

Christian Euler

Microbial Cell Factories, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 22, 2025

Abstract Biomanufacturing offers a potentially sustainable alternative to deriving chemicals from fossil fuels. However, traditional biomanufacturing, which uses sugars as feedstocks, competes with food production and yields unfavourable land use changes, so more options are necessary. Cupriavidus necator is chemolithoautotrophic bacterium capable of consuming carbon dioxide hydrogen sole energy sources, or formate the source both. This autotrophic metabolism makes chemical using C. attractive for biomanufacturing. Additionally, natively fixes in form poly-3-hydroxybutyrate, can be processed make biodegradable plastic. Recent progress development modelling synthetic biology tools have made much usable biomanufacturing chassis. these applications often limited by lack consideration unique physiology metabolic features . As such, further work required better understand intricate mechanisms that allow it prioritise generalization over specialization. In this review, toward physiology-informed engineering across several dimensions critically discussed, recommendations moving physiological approach presented. Arguments specialization, focus on fermentation, -specific tools, goes beyond constraints presented based analysis existing literature.

Language: Английский

Citations

0
The tier system: a host development framework for bioengineering DOI
Chris M. Yeager, Nathan J. Hillson, K. Wozniak

et al.

Current Opinion in Biotechnology, Journal Year: 2025, Volume and Issue: 92, P. 103260 - 103260

Published: Feb. 10, 2025

Language: Английский

Citations

0
Synthetic Biology in Natural Product Biosynthesis DOI
Kaushik Seshadri,

Abner N. D. Abad,

Kyle K. Nagasawa

et al.

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

Synthetic biology has played an important role in the renaissance of natural products research during post-genomics era. The development and integration new tools have transformed workflow product discovery engineering, generating multidisciplinary interest field. In this review, we summarize recent developments biosynthesis from three different aspects. First, advances bioinformatics, experimental, analytical to identify associated with predicted biosynthetic gene clusters (BGCs) will be covered. This followed by extensive review on heterologous expression bacterial, fungal plant organisms. native host-independent paradigm identification, pathway characterization, enzyme is where synthetic most prominent role. Lastly, strategies engineer pathways for structural diversification complexity generation discussed, including assembly-line megasynthase precursor-directed modification, combinatorial biosynthesis.

Language: Английский

Citations

0
Harnessing microalgae as a bioresource for nutraceuticals: advancing bioactive compound exploration and shaping the future of health and functional food innovation DOI Creative Commons

Anjuman Ayub,

Farida Rahayu, Aniswatul Khamidah

et al.

Deleted Journal, Journal Year: 2025, Volume and Issue: 7(5)

Published: April 23, 2025

Language: Английский

Citations

0
Engineering Artificial 5′ Regulatory Sequences for Thermostable Protein Expression in the Extremophile Thermus thermophilus DOI Creative Commons
Che Fai Alex Wong,

S Zhang,

Lisa Tietze

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 6, 2025

ABSTRACT The utilisation of biocatalysts in biotechnological applications often necessitates their heterologous expression suitable host organisms. However, the range standardised microbial hosts for recombinant protein production remains limited, with most being mesophilic and suboptimal certain types. Although thermophilic bacterium Thermus thermophilus has long been established as a valuable extremophile host, thanks to its high-temperature tolerance, robust growth, extensively characterised proteome, genetic toolkit predominantly depended on limited set native promoters. To overcome this bottleneck, we have expanded available regulatory repertoire T. by developing novel artificial 5′ sequences. In study, applied our Gene Expression Engineering platform engineer 53 sequences (ARES) . These ARES, which comprise both promoter untranslated regions (UTRs), were functionally Escherichia coli , revealing distinct host-specific patterns. Furthermore, demonstrated utility these ARES demonstrating high-level thermostable proteins, including β -galactosidase, superfolder citrine fluorescent protein, phytoene synthase. A bioinformatic analysis also carried out indicating that possess markedly lower GC content compared This study contributes expanding providing validated enhancing versatility synthetic biology chassis expression.

Language: Английский

Citations

0
Genomic Modifications of Lactic Acid Bacteria and Their Applications in Dairy Fermentation DOI Creative Commons
Zifan Xie, Olivia McAuliffe, Yong‐Su Jin

et al.

Journal of Dairy Science, Journal Year: 2024, Volume and Issue: 107(11), P. 8749 - 8764

Published: July 3, 2024

Lactic Acid Bacteria (LAB) have a long history of safe use in milk fermentation and are generally recognized as health-promoting microorganisms when present fermented foods. LAB also important components the human intestinal microbiota widely used probiotics. Considering their health-beneficial properties, considered appropriate vehicles that can be genetically modified for food, industrial pharmaceutical applications. Here, this review describes (1) potential opportunities application strains dairy (2) various genomic modification tools strains, such random mutagenesis, adaptive laboratory evolution, conjugation, homologous recombination, recombineering, CRISPR (clustered regularly interspaced short palindromic repeat)- Cas (CRISPR-associated protein) based genome engineering. Lastly, discusses future developments these technologies applications fermentations.

Language: Английский

Citations

3