Cooperative assembly confers regulatory specificity and long-term genetic circuit stability DOI Creative Commons
Meghan D. J. Bragdon, Nikit Patel, James Chuang

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(18), P. 3810 - 3825.e18

Published: Aug. 1, 2023

A ubiquitous feature of eukaryotic transcriptional regulation is cooperative self-assembly between transcription factors (TFs) and DNA cis-regulatory motifs. It thought that this strategy enables specific regulatory connections to be formed in gene networks otherwise weakly interacting, low-specificity molecular components. Here, using synthetic circuits constructed yeast, we find high specificity can emerge from cooperative, multivalent interactions among artificial zinc-finger-based TFs. We show "wired" the TF assembly are effectively insulated aberrant misregulation host cell genome. As demonstrate experiments mathematical models, mechanism sufficient rescue circuit-driven fitness defects, resulting genetic functional stability long-term continuous culture. Our naturally inspired approach offers a simple, generalizable means for building high-fidelity, evolutionarily robust scaled wide range organisms applications.

Language: Английский

Carbon-negative production of acetone and isopropanol by gas fermentation at industrial pilot scale DOI Open Access

Fungmin Liew,

Robert Nogle,

Tanus Abdalla

et al.

Nature Biotechnology, Journal Year: 2022, Volume and Issue: 40(3), P. 335 - 344

Published: Feb. 21, 2022

Language: Английский

Citations

321
High-Throughput Screening Technology in Industrial Biotechnology DOI
Weizhu Zeng, Likun Guo, Sha Xu

et al.

Trends in biotechnology, Journal Year: 2020, Volume and Issue: 38(8), P. 888 - 906

Published: Jan. 28, 2020

Language: Английский

Citations

255
An Overview of Drug Discovery and Development DOI
Nurken Berdigaliyev, Mohamad Aljofan

Future Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 12(10), P. 939 - 947

Published: April 9, 2020

A new medicine will take an average of 10–15 years and more than US$2 billion before it can reach the pharmacy shelf. Traditionally, drug discovery relied on natural products as main source entities, but was later shifted toward high-throughput synthesis combinatorial chemistry-based development. New technologies such ultra-high-throughput screening artificial intelligence are being heavily employed to reduce cost time early discovery, they remain relatively unchanged. However, there other potentially faster cheaper means discovery? Is repurposing a viable alternative? In this review, we discuss different including their advantages disadvantages.

Language: Английский

Citations

254
Machine learning for metabolic engineering: A review DOI Creative Commons
Christopher E. Lawson, Jose Manuel Martí, Tijana Radivojević

et al.

Metabolic Engineering, Journal Year: 2020, Volume and Issue: 63, P. 34 - 60

Published: Nov. 20, 2020

Machine learning provides researchers a unique opportunity to make metabolic engineering more predictable. In this review, we offer an introduction discipline in terms that are relatable engineers, as well providing in-depth illustrative examples leveraging omics data and improving production. We also include practical advice for the practitioner of management, algorithm libraries, computational resources, important non-technical issues. A variety applications ranging from pathway construction optimization, genetic editing cell factory testing, production scale-up discussed. Moreover, promising relationship between machine mechanistic models is thoroughly reviewed. Finally, future perspectives most directions combination disciplines examined.

Language: Английский

Citations

208
Industrial biotechnology of Pseudomonas putida: advances and prospects DOI Creative Commons

Anna Weimer,

Michael Kohlstedt, Daniel C. Volke

et al.

Applied Microbiology and Biotechnology, Journal Year: 2020, Volume and Issue: 104(18), P. 7745 - 7766

Published: Aug. 13, 2020

Abstract Pseudomonas putida is a Gram-negative, rod-shaped bacterium that can be encountered in diverse ecological habitats. This ubiquity traced to its remarkably versatile metabolism, adapted withstand physicochemical stress, and the capacity thrive harsh environments. Owing these characteristics, there growing interest this microbe for industrial use, corresponding research has made rapid progress recent years. Hereby, strong drivers are exploitation of cheap renewable feedstocks waste streams produce value-added chemicals steady genetic strain engineering systems biology understanding bacterium. Here, we summarize advances prospects engineering, synthetic biology, applications P. as cell factory. Key points • global Novel tools enable system-wide streamlined genomic engineering. Applications range from bioeconomy biosynthetic drugs.

Language: Английский

Citations

191
Chemically and Biologically Engineered Bacteria‐Based Delivery Systems for Emerging Diagnosis and Advanced Therapy DOI
Zhaoting Li, Yixin Wang, Jun Liu

et al.

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(38)

Published: Aug. 4, 2021

Abstract Bacteria are one of the main groups organisms, which dynamically and closely participate in human health disease development. With integration chemical biotechnology, bacteria have been utilized as an emerging delivery system for various biomedical applications. Given unique features such their intrinsic biocompatibility motility, bacteria‐based systems drawn wide interest diagnosis treatment diseases, including cancer, infectious kidney failure, hyperammonemia. Notably, at interface biotechnology bacteria, many research opportunities initiated, opening a promising frontier application. Herein, current synergy design principles systems, microbial modulation, clinical translation reviewed, with special focus on advances therapy.

Language: Английский

Citations

175
Dynamic control in metabolic engineering: Theories, tools, and applications DOI Creative Commons
Christopher J. Hartline, Alexander Schmitz, Yichao Han

et al.

Metabolic Engineering, Journal Year: 2020, Volume and Issue: 63, P. 126 - 140

Published: Sept. 11, 2020

Metabolic engineering has allowed the production of a diverse number valuable chemicals using microbial organisms. Many biological challenges for improving bio-production exist which limit performance and slow commercialization metabolically engineered systems. Dynamic metabolic is rapidly developing field that seeks to address these through design genetically encoded control systems allow cells autonomously adjust their flux in response external internal state. This review first discusses theoretical works provide mechanistic insights choices dynamic including two-stage, continuous, population behavior strategies. Next, we summarize molecular mechanisms various sensors actuators enable Finally, important applications several metabolite products are highlighted, fatty acids, aromatics, terpene compounds. Altogether, this provides comprehensive overview progress, advances, prospects improved titer, rate, yield metrics engineering.

Language: Английский

Citations

138
Metabolic Engineering: Methodologies and Applications DOI

Michael Volk,

Vinh Tran, Shih‐I Tan

et al.

Chemical Reviews, Journal Year: 2022, Volume and Issue: 123(9), P. 5521 - 5570

Published: Dec. 30, 2022

Metabolic engineering aims to improve the production of economically valuable molecules through genetic manipulation microbial metabolism. While discipline is a little over 30 years old, advancements in metabolic have given way industrial-level molecule benefitting multiple industries such as chemical, agriculture, food, pharmaceutical, and energy industries. This review describes design, build, test, learn steps necessary for leading successful campaign. Moreover, we highlight major applications engineering, including synthesizing chemicals fuels, broadening substrate utilization, improving host robustness with focus on specific case studies. Finally, conclude discussion perspectives future challenges related engineering.

Language: Английский

Citations

107
Bacterial therapies at the interface of synthetic biology and nanomedicine DOI
Jaeseung Hahn, Suwan Ding, Jongwon Im

et al.

Nature Reviews Bioengineering, Journal Year: 2023, Volume and Issue: 2(2), P. 120 - 135

Published: Oct. 10, 2023

Language: Английский

Citations

44
Relieving metabolic burden to improve robustness and bioproduction by industrial microorganisms DOI Creative Commons
Jiwei Mao, Hongyu Zhang, Yu Chen

et al.

Biotechnology Advances, Journal Year: 2024, Volume and Issue: 74, P. 108401 - 108401

Published: June 27, 2024

Metabolic burden is defined by the influence of genetic manipulation and environmental perturbations on distribution cellular resources. The rewiring microbial metabolism for bio-based chemical production often leads to a metabolic burden, followed adverse physiological effects, such as impaired cell growth low product yields. Alleviating imposed undesirable changes has become an increasingly attractive approach constructing robust factories. In this review, we provide brief overview engineering, focusing specifically recent developments strategies diminishing while improving robustness yield. A variety examples are presented showcase promise engineering in facilitating design construction Finally, challenges limitations encountered discussed.

Language: Английский

Citations

23