Host-aware synthetic biology

Boo, Alice; Ellis, Tom; Stan, Guy‐Bart

doi:10.1016/j.coisb.2019.03.001

Cited by 93 publications

(85 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The last decade has seen synthetic biology recognise the importance of context, be it compositional, intracellular or environmental [7,6]. However, community context has largely been neglected, with the consequence that we have limited ourselves to building systems of single, homogeneous populations that are only capable of functioning in controlled environments.…”

Section: Discussionmentioning

confidence: 99%

Single strain control of microbial consortia

Fedorec

Karkaria

Sulu

et al. 2019

Preprint

View full text Add to dashboard Cite

AbstractThe scale of the biological systems we can engineer is limited by the burden that host cells can bear. Division-of-labour can spread that burden across a community of cells but competitive exclusion inevitably leads to the removal of less fit community members over time. Here, we leverage amensalism and competitive exclusion to stabilise multi-species communities by engineering a strain of Escherichia coli which secretes a toxin in response to competition. We show mathematically and experimentally that such a system can produce stable populations with a composition that is tunable by easily controllable parameters. This is the first system to use competitive exclusion to create a stable two-species consortia and the first to only require the engineering of a single strain.

show abstract

Section: Discussionmentioning

confidence: 99%

Single strain control of microbial consortia

Fedorec

Karkaria

Sulu

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…The comfortable, yet error-prone, assumption that engineered parts alone can ultimately explain phenotypic performance needs to be expanded upon 12 . This leads us to consider what has been termed genetic background 15 and host-aware 16 dynamics: cellular features and constraints that have an impact on circuit performance but are not captured by the DNA sequences of the construct. In recent years, several of these features have been analysed: the impact of having limited cellular resources 37,38 (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Both the burden imposed by synthetic constructs on the host 13,14 and the impact of context on genetic activity 15 , have phenotypic implications that cannot be predicted from a gene-centric standpoint. Recently, the term host-awareness 16,17 has been coined to bring attention to this problem, which is at the core of the lack of part interoperability 18 (i.e., parts that show similar performance in different host contexts).…”

Section: Introductionmentioning

confidence: 99%

Contextual dependencies expand the re-usability of genetic inverters

Tas

Grozinger

Stoof

et al. 2020

Preprint

View full text Add to dashboard Cite

The design and implementation of Boolean logic functions in living cells has become a very active field within synthetic biology. By controlling networks of regulatory proteins, novel genetic circuits are engineered to generate predefined output responses. Although many current implementations focus solely on the genetic components of the circuit, the host context in which the circuit performs is crucial for its outcome. Here, we characterise 20 genetic NOT logic gates (inverters) in up to 7 bacterial-based contexts each, to finally generate 135 different functions. The contexts we focus on are particular combinations of four plasmid backbones and three hosts, two Escherichia coli and one Pseudomonas putida strains. Each NOT logic gate shows seven different logic behaviours, depending on the context. That is, gates can be reconfigured to fit response requirements by changing only contextual parameters. Computational analysis shows that this range of behaviours improves the compatibility between gates, because there are considerably more possibilities for combination than when considering a unique function per genetic construct. Finally, we address the issue of interoperability and portability by measuring, scoring, and comparing gate performance across contexts. Rather than being a limitation, we argue that the effect of the genetic background on synthetic constructs expand the scope of the functions that can be engineered in complex cellular environments, and advocate for considering context as a fundamental design parameter for synthetic biology.

show abstract

“…Significant effortsfor example, to develop greater understanding and control of intracellular and intercellular processes [26,27] . The ability to re-programme different hosts ('chassis') commonly used in industrial fermentations, such as yeast Saccharomyces cerevisiae, will be important.…”

Section: The Bioeconomy Drivermentioning

confidence: 99%

Developing synthetic biology for industrial biotechnology applications

Clarke

Kitney

2020

Biochemical Society Transactions

View full text Add to dashboard Cite

Since the beginning of the 21st Century, synthetic biology has established itself as an effective technological approach to design and engineer biological systems. Whilst research and investment continues to develop the understanding, control and engineering infrastructural platforms necessary to tackle ever more challenging systems — and to increase the precision, robustness, speed and affordability of existing solutions — hundreds of start-up companies, predominantly in the US and UK, are already translating learnings and potential applications into commercially viable tools, services and products. Start-ups and SMEs have been the predominant channel for synthetic biology commercialisation to date, facilitating rapid response to changing societal interests and market pull arising from increasing awareness of health and global sustainability issues. Private investment in start-ups across the US and UK is increasing rapidly and now totals over $12bn. Health-related biotechnology applications have dominated the commercialisation of products to date, but significant opportunities for the production of bio-derived materials and chemicals, including consumer products, are now being developed. Synthetic biology start-ups developing tools and services account for between 10% (in the UK) and ∼25% (in the US) of private investment activity. Around 20% of synthetic biology start-ups address industrial biotechnology targets, but currently, only attract ∼11% private investment. Adopting a more networked approach — linking specialists, infrastructure and ongoing research to de-risk the economic challenges of scale-up and supported by an effective long-term funding strategy — is set to transform the impact of synthetic biology and industrial biotechnology in the bioeconomy.

show abstract

Host-aware synthetic biology

Cited by 93 publications

References 44 publications

Single strain control of microbial consortia

Single strain control of microbial consortia

Contextual dependencies expand the re-usability of genetic inverters

Developing synthetic biology for industrial biotechnology applications

Contact Info

Product

Resources

About