11 results found
Clifford ER, Bradley RW, Wey LT, et al., 2021, Phenazines as model low-midpoint potential electron shuttles for photosynthetic bioelectrochemical systems, Chemical Science, Vol: 12, Pages: 3328-3338, ISSN: 2041-6520
Bioelectrochemical approaches for energy conversion rely on efficient wiring of natural electron transport chains to electrodes. However, state-of-the-art exogenous electron mediators give rise to significant energy losses and, in the case of living systems, long-term cytotoxicity. Here, we explored new selection criteria for exogenous electron mediation by examining phenazines as novel low-midpoint potential molecules for wiring the photosynthetic electron transport chain of the cyanobacterium Synechocystis sp. PCC 6803 to electrodes. We identified pyocyanin (PYO) as an effective cell-permeable phenazine that can harvest electrons from highly reducing points of photosynthesis. PYO-mediated photocurrents were observed to be 4-fold higher than mediator-free systems with an energetic gain of 200 mV compared to the common high-midpoint potential mediator 2,6-dichloro-1,4-benzoquinone (DCBQ). The low-midpoint potential of PYO led to O2 reduction side-reactions, which competed significantly against photocurrent generation; the tuning of mediator concentration was important for outcompeting the side-reactions whilst avoiding acute cytotoxicity. DCBQ-mediated photocurrents were generally much higher but also decayed rapidly and were non-recoverable with fresh mediator addition. This suggests that the cells can acquire DCBQ-resistance over time. In contrast, PYO gave rise to steadier current enhancement despite the co-generation of undesirable reactive oxygen species, and PYO-exposed cells did not develop acquired resistance. Moreover, we demonstrated that the cyanobacteria can be genetically engineered to produce PYO endogenously to improve long-term prospects. Overall, this study established that energetic gains can be achieved via the use of low-potential phenazines in photosynthetic bioelectrochemical systems, and quantifies the factors and trade-offs that determine efficacious mediation in living bioelectrochemical systems.
Bradley R, 2019, Bio-electrical engineering: A promising frontier for synthetic biology, Biochemist, Vol: 41, Pages: 10-13, ISSN: 0954-982X
What do the following have in common? The production of methane gas from farm waste; toilets at a music festival, lit with LED lights; a bacterial biofilm that is on the brink of starvation. All of these involve microbes that are making use of bio-electrical processes. Though it is difficult to define the limits of what can be called bio-electrical, these processes are typically responding to or creating a current or voltage, with the electrical effects extending beyond the limit of an individual cell. In the examples above, current is flowing between organisms of different species or between an organism and an abiotic material, or voltage changes are being sensed and propagated across a colony of cells. Our appreciation of the extent of electrical phenomena in microbial biology has seen a recent revival, with studies revealing not just the variety of bioelectrical processes that exist but also defining the molecular mechanisms responsible. Now, we can begin to apply the approaches and techniques of synthetic biology. By re-engineering natural systems, we can hope to improve our understanding of how their components function and repurpose them for exciting biotechnological applications.
Bradley RW, Buck M, Wang B, 2016, Recognizing and engineering digital-like logic gates and switches in gene regulatory networks, Current Opinion in Microbiology, Vol: 33, Pages: 74-82, ISSN: 1879-0364
A central aim of synthetic biology is to build organisms that can perform useful activities in response to specified conditions. The digital computing paradigm which has proved so successful in electrical engineering is being mapped to synthetic biological systems to allow them to make such decisions. However, stochastic molecular processes have graded input-output functions, thus, bioengineers must select those with desirable characteristics and refine their transfer functions to build logic gates with digital-like switching behaviour. Recent efforts in genome mining and the development of programmable RNA-based switches, especially CRISPRi, have greatly increased the number of parts available to synthetic biologists. Improvements to the digital characteristics of these parts are required to enable robust predictable design of deeply layered logic circuits.
Bradley RW, Buck M, Wang B, 2015, Tools and principles for microbial gene circuit engineering., Journal of Molecular Biology, Vol: 428, Pages: 862-888, ISSN: 1089-8638
Synthetic biologists aim to construct novel genetic circuits with useful applications through rational design and forward engineering. Given the complexity of signal processing that occurs in natural biological systems, engineered microbes have the potential to perform a wide range of desirable tasks that require sophisticated computation and control. Realising this goal will require accurate predictive design of complex synthetic gene circuits and accompanying large sets of quality modular and orthogonal genetic parts. Here we present a current overview of the versatile components and tools available for engineering gene circuits in microbes, including recently developed RNA-based tools that possess large dynamic ranges and can be easily programmed. We introduce design principles that enable robust and scalable circuit performance such as insulating a gene circuit against unwanted interactions with its context, and we describe efficient strategies for rapidly identifying and correcting causes of failure and fine-tuning circuit characteristics.
Bradley R, Wang B, 2015, Designer cell signal processing circuits for biotechnology, New Biotechnology, ISSN: 1871-6784
Microorganisms are able to respond effectively to diverse signals from their environment and internal metabolism because they possess a sophisticated information processing capacity. A central aim of synthetic biology is to control and reprogramme the signal processing pathways within living cells so as to realise repurposed, beneficial applications ranging from disease diagnosis and environmental sensing to chemical bioproduction. Up to now most examples of synthetic biological signal processing have been built based on digital information flow, though analogue computing is being developed to cope with more complex operations and larger sets of variables. Great progress has been made in expanding the categories of characterised biological components that can be used for cellular signal manipulation, thereby allowing synthetic biologists to more rationally programme increasingly complex behaviours into living cells. Here we provide an overview of the components and strategies that exist for designer cell signal processing and decision making, discuss how these have been implemented in prototype systems for therapeutic, environmental, and industrial biotechnological applications, and examine emerging challenges in this promising field.
McCormick AJ, Bombelli P, Bradley RW, et al., 2015, Biophotovoltaics: oxygenic photosynthetic organisms in the world of bioelectrochemical systems, ENERGY & ENVIRONMENTAL SCIENCE, Vol: 8, Pages: 1092-1109, ISSN: 1754-5692
McCormick AJ, Bombelli P, Lea-Smith DJ, et al., 2013, Hydrogen production through oxygenic photosynthesis using the cyanobacterium Synechocystis sp PCC 6803 in a bio-photoelectrolysis cell (BPE) system, ENERGY & ENVIRONMENTAL SCIENCE, Vol: 6, Pages: 2682-2690, ISSN: 1754-5692
Bradley RW, Bombelli P, Lea-Smith DJ, et al., 2013, Terminal oxidase mutants of the cyanobacterium Synechocystis sp PCC 6803 show increased electrogenic activity in biological photo-voltaic systems, PHYSICAL CHEMISTRY CHEMICAL PHYSICS, Vol: 15, Pages: 13611-13618, ISSN: 1463-9076
Bradley RW, Bombelli P, Rowden SJL, et al., 2012, Biological photovoltaics: intra- and extra-cellular electron transport by cyanobacteria, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 40, Pages: 1302-1307, ISSN: 0300-5127
Bombelli P, Bradley RW, Scott AM, et al., 2011, Quantitative analysis of the factors limiting solar power transduction by Synechocystis sp. PCC 6803 in biological photovoltaic devices, ENERGY & ENVIRONMENTAL SCIENCE, Vol: 4, Pages: 4690-4698, ISSN: 1754-5692
Bombelli P, McCormick A, Bradley R, et al., 2011, Harnessing solar energy by bio-photovoltaic (BPV) devices., Commun Agric Appl Biol Sci, Vol: 76, Pages: 89-91, ISSN: 1379-1176
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