ORCID Profile
0000-0002-0594-3441
Current Organisation
Macquarie University
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Biochemistry and Cell Biology | Synthetic Biology |
Expanding Knowledge in the Biological Sciences | Environmentally Sustainable Manufacturing not elsewhere classified
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.YMBEN.2015.03.008
Abstract: Some of the most productive metabolic engineering strategies involve genetic modifications that cause severe metabolic burden on the host cell. Growth-limiting genetic modifications can be more effective if they are 'switched on' after a population growth phase has been completed. To address this problem we have engineered dynamic regulation using a previously developed synthetic quorum sensing circuit in Saccharomyces cerevisiae. The circuit autonomously triggers gene expression at a high population density, and was linked with an RNA interference module to enable target gene silencing. As a demonstration the circuit was used to control flux through the shikimate pathway for the production of para-hydroxybenzoic acid (PHBA). Dynamic RNA repression allowed gene knock-downs which were identified by elementary flux mode analysis as highly productive but with low biomass formation to be implemented after a population growth phase, resulting in the highest published PHBA titer in yeast (1.1mM).
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.CBPA.2017.05.017
Abstract: Isoprenoids (terpenes/terpenoids) have many useful industrial applications, but are often not produced at industrially viable level in their natural sources. Synthetic biology approaches have been used extensively to reconstruct metabolic pathways in tractable microbial hosts such as yeast and re-engineer pathways and networks to increase yields. Here we review recent advances in this field, focusing on central carbon metabolism engineering to increase precursor supply, re-directing carbon flux for production of C10, C15, or C20 isoprenoids, and chemical decoration of high value diterpenoids (C20). We also overview other novel synthetic biology strategies that have potential utility in yeast isoprenoid pathway engineering. Finally, we address the question of what is required in the future to move the field forwards.
Publisher: Springer Science and Business Media LLC
Date: 04-2015
Publisher: Springer Science and Business Media LLC
Date: 15-01-2021
DOI: 10.1038/S41467-020-20764-2
Abstract: The practices of synthetic biology are being integrated into ‘multiscale’ designs enabling two-way communication across organic and inorganic information substrates in biological, digital and cyber-physical system integrations. Novel applications of ‘bio-informational’ engineering will arise in environmental monitoring, precision agriculture, precision medicine and next-generation biomanufacturing. Potential developments include sentinel plants for environmental monitoring and autonomous bioreactors that respond to biosensor signaling. As bio-informational understanding progresses, both natural and engineered biological systems will need to be reimagined as cyber-physical architectures. We propose that a multiple length scale taxonomy will assist in rationalizing and enabling this transformative development in engineering biology.
Publisher: MDPI AG
Date: 26-07-2018
DOI: 10.3390/GENES9080375
Abstract: Biosensors are enabling major advances in the field of analytics that are both facilitating and being facilitated by advances in synthetic biology. The ability of biosensors to rapidly and specifically detect a wide range of molecules makes them highly relevant to a range of industrial, medical, ecological, and scientific applications. Approaches to biosensor design are as erse as their applications, with major biosensor classes including nucleic acids, proteins, and transcription factors. Each of these biosensor types has advantages and limitations based on the intended application, and the parameters that are required for optimal performance. Specifically, the choice of biosensor design must consider factors such as the ligand specificity, sensitivity, dynamic range, functional range, mode of output, time of activation, ease of use, and ease of engineering. This review discusses the rationale for designing the major classes of biosensor in the context of their limitations and assesses their suitability to different areas of biotechnological application.
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.TIBTECH.2016.02.002
Abstract: Synthetic biology has progressed to the point where genes that encode whole metabolic pathways and even genomes can be manufactured and brought to life. This impressive ability to synthesise and assemble DNA is not yet matched by an ability to predictively engineer biology. These difficulties exist because biological systems are often overwhelmingly complex, having evolved to facilitate growth and survival rather than specific engineering objectives such as the optimisation of biochemical production. A promising and revolutionary solution to this problem is to harness the process of evolution to create microbial strains with desired properties. The tools of systems biology can then be applied to understand the principles of biological design, bringing synthetic biology closer to becoming a predictive engineering discipline.
Publisher: American Society for Microbiology
Date: 15-05-2015
DOI: 10.1128/AEM.04144-14
Abstract: Monoterpenes are liquid hydrocarbons with applications ranging from flavor and fragrance to replacement jet fuel. Their toxicity, however, presents a major challenge for microbial synthesis. Here we evolved limonene-tolerant Saccharomyces cerevisiae strains and sequenced six strains across the 200-generation evolutionary time course. Mutations were found in the tricalbin proteins Tcb2p and Tcb3p. Genomic reconstruction in the parent strain showed that truncation of a single protein (tTcb3p 1-989 ), but not its complete deletion, was sufficient to recover the evolved phenotype improving limonene fitness 9-fold. tTcb3p 1-989 increased tolerance toward two other monoterpenes (β-pinene and myrcene) 11- and 8-fold, respectively, and tolerance toward the biojet fuel blend AMJ-700t (10% cymene, 50% limonene, 40% farnesene) 4-fold. tTcb3p 1-989 is the first ex le of successful engineering of phase tolerance and creates opportunities for production of the highly toxic C 10 alkenes in yeast.
Publisher: Springer Science and Business Media LLC
Date: 11-03-2021
Publisher: Springer Science and Business Media LLC
Date: 04-11-2020
DOI: 10.1038/S41467-020-19390-9
Abstract: Utilising one-carbon substrates such as carbon dioxide, methane, and methanol is vital to address the current climate crisis. Methylotrophic metabolism enables growth and energy generation from methanol, providing an alternative to sugar fermentation. Saccharomyces cerevisiae is an important industrial microorganism for which growth on one-carbon substrates would be relevant. However, its ability to metabolize methanol has been poorly characterised. Here, using adaptive laboratory evolution and 13 C-tracer analysis, we discover that S. cerevisiae has a native capacity for methylotrophy. A systems biology approach reveals that global rearrangements in central carbon metabolism fluxes, gene expression changes, and a truncation of the uncharacterized transcriptional regulator Ygr067cp supports improved methylotrophy in laboratory evolved S. cerevisiae . This research paves the way for further biotechnological development and fundamental understanding of methylotrophy in the preeminent eukaryotic model organism and industrial workhorse, S. cerevisiae .
Publisher: Springer Science and Business Media LLC
Date: 19-10-2022
DOI: 10.1038/S41467-022-33974-7
Abstract: Human enterprises through the solar system will entail long-duration voyages and habitation creating challenges in maintaining healthy diets. We discuss consolidating multiple sensory and nutritional attributes into microorganisms to develop customizable food production systems with minimal inputs, physical footprint, and waste. We envisage that a yeast collection bioengineered for one-carbon metabolism, optimal nutrition, and erse textures, tastes, aromas, and colors could serve as a flexible food-production platform. Beyond its potential for supporting humans in space, bioengineered microbial-based food could lead to a new paradigm for Earth’s food manufacturing that provides greater self-sufficiency and removes pressure from natural ecosystems.
Publisher: Springer Science and Business Media LLC
Date: 26-06-2015
Publisher: Cold Spring Harbor Laboratory
Date: 23-07-2022
DOI: 10.1101/2022.07.22.501046
Abstract: We have designed, constructed, and debugged a synthetic 753,096 bp version of Saccharomyces cerevisiae chromosome XIV as part of the international Sc2.0 project. We showed that certain synthetic loxPsym recombination sites can interfere with mitochondrial protein localization, that the deletion of one intron ( NOG2 ) reduced fitness, and that a reassigned stop codon can lead to a growth defect. In parallel to these rational debugging modifications, we used Adaptive Laboratory Evolution to generate a general growth defect suppressor rearrangement in the form of increased TAR1 copy number. We also extended the utility of the Synthetic Chromosome Recombination and Modification by LoxP-mediated Evolution (SCRaMbLE) system by engineering synthetic-wild-type tetraploid hybrid strains that buffer against essential gene loss. The presence of wild-type chromosomes in the hybrid tetraploids increased post-SCRaMbLE viability and heterologous DNA integration, highlighting the plasticity of the S. cerevisiae genome in the presence of rational and non-rational modifications.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8TB00994E
Abstract: Light-triggered endolysosomal escape enhances gene delivery by photoresponsive LPD nanoparticles.
Publisher: American Chemical Society (ACS)
Date: 18-07-2022
DOI: 10.1021/ACSSYNBIO.2C00110
Abstract: The global expansion of biomanufacturing is currently limited by the availability of sugar-based microbial feedstocks, which require farmland for cultivation and therefore cannot support large increases in production without impacting the human food supply. One-carbon feedstocks, such as methanol, present an enticing alternative to sugar because they can be produced independently of arable farmland from organic waste, atmospheric carbon dioxide, and hydrocarbons such as biomethane, natural gas, and coal. The development of efficient industrial microorganisms that can convert one-carbon feedstocks into valuable products is an ongoing challenge. This review discusses progress in the field of synthetic methylotrophy with a focus on how it pertains to the important industrial yeast,
Publisher: Wiley
Date: 21-10-2020
DOI: 10.1002/BIT.27591
Publisher: Elsevier BV
Date: 12-2016
Publisher: Springer Science and Business Media LLC
Date: 23-04-2019
Publisher: Elsevier BV
Date: 12-2019
Publisher: Wiley
Date: 13-01-2017
Publisher: American Chemical Society (ACS)
Date: 30-08-2023
Publisher: Springer Science and Business Media LLC
Date: 24-06-2022
DOI: 10.1038/S41467-022-31305-4
Abstract: The Synthetic Yeast Genome Project ( Sc 2.0) represents the first foray into eukaryotic genome engineering and a framework for designing and building the next generation of industrial microbes. However, the laboratory strain S288c used lacks many of the genes that provide phenotypic ersity to industrial and environmental isolates. To address this shortcoming, we have designed and constructed a neo-chromosome that contains many of these erse pan-genomic elements and which is compatible with the Sc 2.0 design and test framework. The presence of this neo-chromosome provides phenotypic plasticity to the Sc 2.0 parent strain, including expanding the range of utilizable carbon sources. We also demonstrate that the induction of programmable structural variation (SCRaMbLE) provides genetic ersity on which further adaptive gains could be selected. The presence of this neo-chromosome within the Sc 2.0 backbone may therefore provide the means to adapt synthetic strains to a wider variety of environments, a process which will be vital to transitioning Sc 2.0 from the laboratory into industrial applications.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.TIBTECH.2021.05.001
Abstract: The creative destruction caused by the coronavirus pandemic is yielding immense opportunity for collaborative innovation networks. The confluence of biosciences, information sciences, and the engineering of biology, is unveiling promising bioinformational futures for a vibrant and sustainable bioeconomy. Bioinformational engineering, underpinned by DNA reading, writing, and editing technologies, has become a beacon of opportunity in a world paralysed by uncertainty. This article draws on lessons from the current pandemic and previous agricultural blights, and explores bioinformational research directions aimed at future-proofing the grape and wine industry against biological shocks from global blights and climate change.
Publisher: American Chemical Society (ACS)
Date: 07-01-2013
DOI: 10.1021/SB300110B
Abstract: Population-density-dependent control of gene expression, or quorum sensing, is widespread in nature and is used to coordinate complex population-wide phenotypes through space and time. We have engineered quorum sensing in S. cerevisiae by rewiring the native pheromone communication system that is normally used by haploid cells to detect potential mating partners. In our system, populations consisting of only mating type "a" cells produce and respond to extracellular α-type pheromone by arresting growth and expressing GFP in a population-density-dependent manner. Positive feedback quorum sensing dynamics were tuned by varying α-pheromone production levels using different versions of the pheromone-responsive FUS1 promoter as well as different versions of pheromone genes (mfα1 or mfα2). In a second system, pheromone communication was rendered conditional upon the presence of aromatic amino acids in the growth medium by controlling α-pheromone expression with the aromatic amino acid responsive ARO9 promoter. In these circuits, pheromone communication and response could be fine-tuned according to aromatic amino acid type and concentration. The genetic control programs developed here are responsive to dynamic spatiotemporal and chemical cellular environments, resulting in up-regulation of gene expression. These programs could be used to control biochemical pathways for the production of fuels and chemicals that are toxic or place a heavy metabolic burden on cell growth.
Publisher: Oxford University Press (OUP)
Date: 2017
Abstract: Biosensors are valuable and versatile tools in synthetic biology that are used to modulate gene expression in response to a wide range of stimuli. Ligand responsive transcription factors are a class of biosensor that can be used to couple intracellular metabolite concentration with gene expression to enable dynamic regulation and high-throughput metabolite producer screening. We have established the Saccharomyces cerevisiae WAR1 transcriptional regulator and PDR12 promoter as an organic acid biosensor that can be used to detect varying levels of para-hydroxybenzoic acid (PHBA) production from the shikimate pathway and output green fluorescent protein (GFP) expression in response. The dynamic range of GFP expression in response to PHBA was dramatically increased by engineering positive-feedback expression of the WAR1 transcriptional regulator from its target PDR12 promoter. In addition, the noise in GFP expression at the population-level was controlled by normalising GFP fluorescence to constitutively expressed mCherry fluorescence within each cell. These biosensor modifications increased the high-throughput screening efficiency of yeast cells engineered to produce PHBA by 5,000-fold, enabling accurate fluorescence activated cell sorting isolation of producer cells that were mixed at a ratio of 1 in 10,000 with non-producers. Positive-feedback, ratiometric transcriptional regulator expression is likely applicable to many other transcription-factor romoter pairs used in synthetic biology and metabolic engineering for both dynamic regulation and high-throughput screening applications.
Publisher: MDPI AG
Date: 10-07-2018
DOI: 10.3390/GENES9070348
Publisher: Springer Science and Business Media LLC
Date: 08-04-2023
DOI: 10.1038/S41467-023-37748-7
Abstract: Naturally evolved organisms typically have large genomes that enable their survival and growth under various conditions. However, the complexity of genomes often precludes our complete understanding of them, and limits the success of biotechnological designs. In contrast, minimal genomes have reduced complexity and therefore improved engineerability, increased biosynthetic capacity through the removal of unnecessary genetic elements, and less recalcitrance to complete characterisation. Here, we review the past and current genome minimisation and re-functionalisation efforts, with an emphasis on the latest advances facilitated by synthetic genomics, and provide a critical appraisal of their potential for industrial applications.
Start Date: 08-2022
End Date: 07-2025
Amount: $494,550.00
Funder: Australian Research Council
View Funded ActivityStart Date: 05-2020
End Date: 12-2023
Amount: $553,035.00
Funder: Australian Research Council
View Funded Activity