Weeding the Gems

HVCfP Workshop on Synthetic Biology

The High Value Chemicals from Plants (HVCfP) network is a BBSRC-funded consortium that aims to support the development of resources that will enable researchers to investigate different avenues to produce commercially relevant compounds from plants. These strategies might take advantage of naturally occurring novel biochemical pathways or use plant systems to produce heterologous products of commercial interest. This network is based at the University of York and led by Professor Ian Graham and by Professor Anna Osbourn (John Innes Centre). In their past research both these network-leaders have investigated the potential for increasing the production of high value chemicals, namely the anti-malarial compound Artesmisia or the defence-saponin Avenacin.

On July 13^th and 14^th the HVCfP network hosted a meeting in Dunston Hall, near Norwich that aimed to assess the potential of using synthetic biology (synbio) approaches in the production of high value chemicals. The use of synthetic biology is a key component of the growing bioeconomy, which aims to unlock the potential of biological systems for the production of useful compounds. Synbio was named as one of the governments ‘Eight great technologies’ and the subject of the RCUK ‘Synthetic Biology roadmap’. Principles of synbio encompass engineering molecular and metabolic systems for the economic and pastoral benefit of society. Although synthetic biology has largely been focused on single-celled experimental systems there is clear potential to transfer this technology to plants, as exemplified by the production of flu-vaccine in tobacco.

‘High value’ chemicals in plants are usually produced at low levels and/or in organisms that are currently not amenable to transgenic or synthetic biology procedures. Therefore at the start of this meeting it seemed that there was too much of a distance between principles of synbio and the production of high value chemicals for meaningful discussions to occur. However the meeting was structured in such a way to make it clear that there is not such the disconnect as initially thought, even though there is a long way to go until many of the goals are realized. The full meeting schedule can be obtained from Wendy Lawley.

The first session provided an overview to synthetic biology with Jim Haseloff (Cambridge) introducing general principles of the topic, including some work on the new ‘chassis’ that his lab are using for synbio, the liverwort Marchantia Polymorpha. Rowan McKibbin from the BBSRC then explained that the research councils continue to be committed to synbio as highlighted by a ‘refreshment’ of the Synthetic Biology Roadmap in coming months.

Latterly Joyce Tait (Edinburgh) provided an overview of the future ethical considerations that synthetic biologists might need to consider. Her overall message was that in terms of public acceptance of the technology, synthetic biology is currently in a strong position. Notably it differs from the debate with genetic modification in a number of critical ways 1. Most of the products from synbio are not food-stuffs and 2. The technology is not linked to multinational companies in the same way as, for example, GMO crops. However Kate Miller (Nottingham) made the important cautionary point that few members of the public have actually heard about synthetic biology at this point and so opinions might change….

Session Two focused on some of the technologies involved in synthetic biology. As Head of Synthetic Biology at The Sainsbury lab, Nicola Patron presented ideas about  standardization of molecular parts for use in synbio, highlighting a new paper in New Phytologist that attempts to develop a ‘common syntax for DNA parts in synthetic biology’ . The GARNet blog will have more on this paper in coming weeks but in short, it aims to bring together the community so that transfer of materials will be more routine in future.

Arguably the most striking presentation of the day was from Patrick Cai from the Edinburgh Genome Foundry who introduced approaches that have been developed in the multinational Synthetic Yeast 2.0 project. These include the construction of synthetic yeast chromosomes and attempts to SCRaMbLE the yeast genome, each of which have the grand goal of attempting to re-define what it takes to be a eukaryotic ‘genome’.

The session continued strongly with a classification-redefining presentation from Matias Zurbriggen (Freiburg) who demonstrated the feasibility of recapitulating auxin and light signaling in mammalian cell lines, with the aim of developing general molecular sensors. Marnix Medema (Wageningen) demonstrated the power of a bioinformatic approach to discover biosynthetic pathways in non-model organisms, which might be a critical technology in plants that produce important secondary metabolites.

The first plant image of the workshop appeared courtesy of Sarah O’Connor (JIC) who presented the Madagascar Periwinkle, which produces important monoterpene indole alkaloids.One of the strengths of this meeting was the breadth of ‘experimental chassis’ that were discussed. These ranged from conventional model organisms such a Saccharomyces cerevisae or Arabidopsis thaliana through the less widely used tobacco, microalgae or Dictyostelium and ultimately to plants such as Madagascar periwinkle or Dioscorea (Yam), whose potential is now being investigated due to the novel compounds they are able to produce.

The second day of talks had a more practical edge as Session Three looked at ‘Production Platforms’ currently in place including use of microalgae, tobacco or E.coli. Anil Day (University of Manchester) introduced the benefits of chloroplast expression, either of individual genes or as fusions to the large subunit of Rubisco. This technology appears to have great potential yet it is striking that no transplastomically-transformed plants have been licensed for growth. Dr Day thought that this is due to regulatory and not technological problems. However it was conceded that one potential problem with this approach is the current inability to transform monocots.

The final session of the workshop focused on ‘Metabolic Engineering’ where examples were given for the output and potential of different systems. Jon Marles-Wright (Edinburgh) discussed engineering bacterial nano- and micro-compartments for different applications. He highlighted three potential benefits: 1. They can protect enzymes from high-temperatures or non-physiological conditions, 2. They can safely hold toxins within cells and 3. They can carry heavy metals. However the challenge is now to go from basic research to develop an ‘Encapsulation Platform’. Watch this space…

Arguably the most ‘complete’ story was presented by Olga Sayanova who described a decade-long journey to move production of fish oils from algae into camelina. This has been a cause-celebre in recent years and an exciting exemplar of what is possible with GM technology. Olga did have some cautionary words about the potential of synthetic biology as ‘one-module’ might not fit all. The heterologous expression of algal genes worked fine in Camelina (just a ‘big Arabidopsis’) but did not work in Flax/Linseed. This highlights that each experimental ‘chassis’ might require their own set of molecular tools to enable expression of your product of interest.

Overall the meeting seemed to be a great success with researchers across a range of disciplines learning plenty outside of their comfort zones. It might be a many years until we are able to produce Galanthamine (or similarly complex molecules) in E.coli but the potential is there to move in that direction….

In addition to discussions of HVCfP, approximately 30 attendees were able to take advantage of a Science-Art-Writing workshop over dinner. This JIC-based initiative is led by Jenni Rant and Anne Osbourn with the aim of linking science and art to enthuse schoolchildren about scientific topics. After general discussions about the topic, the attendees were encouraged to write an original ‘ode or haiku’ about synthetic biology and then to blindly draw their table-mates (two representations of your author are below…), which led to great hilarity all around.

However the important message was that seemingly-disparate topics can be brought together to aid education. Hopefully the workshop attendees were given food for thought concerning their next pubic outreach engagement.

I will finish with my indifferently-received ‘Ode to Plant Synthetic Biology’:

O GREEN MACHINE.