Synthetic Biology Tools
We have developed a variety of synthetic biology tools to facilitate metabolic engineering in both yeast and E. coli, e.g.: plasmid vectors for gene expression, vectors for integration of large amounts of DNA onto the chromosome, engineered protein tools to avoid metabolic carbon competition at key flux points, and synthetic genetic circuits. See the ‘Resources‘ tab for more information, available plasmids etc.
Isoprenoid Pathway Engineering
Isoprenoids are a very large class of natural products. Their chemical and structural diversity lends them to a wide variety of industrial applications (e.g. as pharmaceuticals, biofuels, rubbers, nutraceuticals, agricultural chemicals, flavours, fragrances, colorants, etc.). They are produced in living cells by two distinct metabolic pathways: the well-known mevalonate (MVA) pathway, which is responsible for production of sterols and related compounds, and the recently-discovered methylerythritol phosphate (MEP) pathway. We are using synthetic biology engineering approaches to improve carbon flux through both of these pathways for production of industrially-useful isoprenoids. The aim of this program is to increase conversion of bioprocess feedstocks (such as sucrose – see ‘Feedstock Pathway Engineering’ below) into the desired end product by whole cell bio-catalysts. We have reconstructed synthetic pathways with improved flux in both yeast and E. coli. We have also developed novel approaches to minimise carbon loss to competing pathways, redirect carbon into the desired pathways, and scavenge carbon lost to nonspecific reactions.
Isoprenoid Biofuels and Industrial Biochemicals
We are interested in a large variety of industrially-useful isoprenoids. Examples include isoprene, a C5 hydrocarbon that can be polymerised to make synthetic rubber; various C10 (monoterpene) and C15 (sesquiterpene) hydrocarbons that can be used to produce bio-jet fuel/bio-diesel and have a wide range of other industrial applications; and the strigolactone class of plant hormones, which have a variety of potential industrial applications. Production of these compounds is non-trivial, since they are not naturally made by E. coli and yeast. In particular, for monoterpenes the C10 precursor is typically not available, and must be engineered. Of course, availability of sufficient precursors for bulk production requires substantial engineering of upstream pathways (see above).
Beer Systems Biology: BeerOmics
We use systems biology (yeast genomics, metabolomics and proteomics) to investigate interactions between barley, hops, yeast, and process conditions throughout the brewing process. These interactions are critical for a number of different beer quality traits. We collaborate with Dr Ben Schulz at UQ School of Chemistry and Molecular Biology for beer proteomics.
Biogenic Isoprene Emission
Isoprene is a volatile 5-carbon hydrocarbon emitted by many plant species. It is highly reactive, and is produced in such large quantities from the biosphere that it substantially affects the oxidising potential of the atmosphere. In addition, plants can loose relatively large amounts of carbon and energy during formation of isoprene. We assume that this loss is supported by a biological benefit. I am investigating the biological role of isoprene emission using both plants and model microbes. Tobacco, which does not normally synthesise isoprene, has been engineered to produce isoprene by introduction of an isoprene synthase gene. These plants produce high levels of isoprene and display typical emission responses as observed in normally-emitting plant species. Using these plants, along with azygous control plants, the biological role(s) of isoprene can be examined.In addition to its interesting biological role, isoprene is also of interest as an industrial product due to its application for production of synthetic rubbers. We are therefore also examining production of isoprene in microbial systems.
Feedstock Pathway Engineering
For production of bulk biochemicals using microbes, the carbon source is the key cost driver. Sucrose from sugarcane is preferable to corn-derived glucose as a carbon source because (1) it is highly abundant (2) sugarcane has a very high energy yield per hectare compared to corn (3) sugar is not a staple food crop, and (4) waste biomass can be used to produce electricity, making processes cheaper and more carbon-friendly. Sucrose is a major agricultural product in Australia. However, most industrial strains of E. coli cannot utilise it as a carbon source. To better understand sucrose utilisation, we sequenced the genome of a sucrose-utilising E. coli strain and generated an in silico genome-scale metabolic model. We then developed methods to improve sucrose utilisation in this strain, and to reproducibly engineer efficient sucrose utilisation in industrial E. coli strains. Engineered strains producing polyhydroxybutyrate (a polymer that can be used to make biodegradeable plastics) and peptide bio-surfactants make as much or more bio-product when growing on sucrose than on glucose.
Kimberley Baobab Project
The Australian baobab tree (Adansomia gregorii), is found in the Kimberley region of north-western Australia. Interestingly, the geographical distribution of the Kimberley species overlaps almost perfectly with a particular type of ancient rock art known as Bradshaw paintings. The aetiology of these painting is under hot debate: some maintain that they are part of the extensive Aboriginal rock art found across Australia, and some maintain that these images were painted by a distinct culture which no longer survives in Australia. What is clear is that these paintings are significantly different from other rock art in Australia in terms of style and materials used. The geographical commonality shared between the paintings and the baobab trees prompted us examine more closely the genetic heritage of the baobab tree, in hope of uncovering information about its arrival in Australia.
Jack Pettigrew (Emeritus Professor, The University of Queensland) heads this project
More detail here