Elements of Bioremediation, Biomanufacturing & Bioenergy (E3B): Metals in Biology

The UK is well resourced with the multidisciplinary research skills needed to exploit metal-related biological processes in Biomanufacturing and in Bioenergy production. Demand for Metals in Biology expertise in these sectors is growing in concert with increased awareness (i) that more than a half of all Industrial Bioprocesses are likely to directly involve metalloproteins with most of the remainder being indirectly dependent upon metalloproteins, and (ii) that there is scope to increase competitiveness by optimising metalation and by tuning the catalytic activities of metal centres. This phase II E3B network will initiate new Academic-Industry collaborations in these sectors and encourage the migration of research and development instigated by the phase I Metals in Biology (MiB) BBSRC NIBB to higher technology readiness levels (TRLs).

The phase I MiB BBSRC NIBB funded a dozen projects related to the Bioremediation and Biorecovery of valuable metals. The UK has considerable expertise in bioleaching and downstream metal recovery using bacterial, fungal and plant systems. For example, metal-reducing bacteria can be targeted to a wide range of high valence metals, with scope to precipitate them as valuable metallic nanoparticles with applications as catalysts, nanomagnets, targeted remediation agents (for metals and organics) and quantum dot materials. Bioremediation will therefore be a sector targeted by the phase II E3B network "but only where this leads to the recovery of valuable metals". A diversity of waste materials and waste streams will be targeted, industrial scale-up and process economics (including life cycle analysis) optimised. About a half of polluted sites in the UK that require remediation are contaminated with metals, or a combination of metals and organics. Bio-transformed bio-recovered metals (in catalytic nanoparticles or metalloenzymes) may also be used to remediate sites exclusively contaminated with organics, and a wide range of UK and international industries produce metal-contaminated effluents and residues. The E3B BBSRC NIBB will exploit this largely untapped resource.

The network will run for 5 years and will take advantage of infrastructure, governance and experience gained under phase I MiB. These include (amongst others) the infrastructure to award and manage small grants and contacts (compliant with GDPR).

The outcomes of phase I MiB (diversity of new collaborations, breadth and scale of membership, matching/other funding generated, jobs created or safeguarded, patents awarded, papers published, products launched) provide evidence of the ongoing potential for success of the E3B network and hence give a high degree of confidence that the E3B aims and objectives will be realised.

Examples of 'potential' consortia to advance TRLs include:

Improved hemylation and use of heme-enzymes to manufacture high-value products.

The manufacture of vitamin B12 for industrial biotechnology and for sustainable nutrition.

Bio-recovery of metals in high-value complexes from contaminated wastes.

The free energies of intracellular metals for sustainable consumer goods manufacture.

Intracellular availability of metals for quality control in the manufacture of biologics.

Optimising trace metals in the manufacture of sources of bioenergy.

Final reports show that almost all partnerships (> 90%) funded by MiB phase I are sustaining their Academic-Industry collaboration and/or are eager to find the means to do so, with many testimonials to this effect. For example, the Industrial partner of the final collaboration funded (October 2017) under MiB phase I wrote the following: "So far the development of the LPMOs has progressed very swiftly and we are excited to see the next steps in this project as it has a great potential." In common with most MiB phase I projects, this was a new Academic-Industry collaboration which E3B will progress to higher TRLs.

The prevalence of metallo-enzymes (47% if that the sub-set for which there are structures are representative of the whole) means that a large proportion of bio-industries depend directly, or indirectly, on the catalytic activities of metal-sites. Bioinorganic chemists have become expert in tuning and optimising such sites to drive required reactions. Some metals form more stable complexes with proteins than do others, often by millions of orders of magnitude. To populate some proteins with competitive metals and others with less competitive metals, cells have elaborate systems that precisely control the relative availabilities of different elements, in effect 'levelling the playing field' to support the diversity of vital metalation-reactions. Biochemists have learnt how to measure these crucial metal availabilities in different cell types making it possible to identify when an enzyme is prone to mis-metalation or under-metalation in a heterologous host, or when a cell is grown under process conditions. In turn, this allows cell biologists to manipulate the culture conditions, or molecular biologists to manipulate the host cell, to optimise metalation. Network members will work with the bio-manufacturing and bioenergy sectors to enhance metalation and provide consistent product quality and yield. About a half of wastes are contaminated with metals (often in conjunction with inorganic compounds) and environmental biologists can not only bio-remediate but also bio-recover the metals in valuable forms such as catalytic metal nanoparticles. Members will collaborate with multiple companies to manipulate metallo-enzymes and to optimise metal uptake and assimilation into biomolecules required for bio-energy production, bioremediation, biomedicine and synthesis of high value products. This network will consolidate the activities of communities working on Metals in Biology and accelerate the exploitation of research relevant to industrial biotechnology and bioenergy.

The contributions of the network to Industrial Biotechnology and Bioenergy are pervasive due to the ubiquity of Metals in Biology (metalloenzymes and their metal-supply) and categorised under the following headings:

(A) Metal bioremediation with recovery of valuable metals

(B) Metal-related advances in bio-manufacturing

(C) Metals in bioenergy production

The E3B network will promote interactions between the multidisciplinary Metals in Biology research community and non-Academic beneficiaries.

Descriptions of the projects supported in MiB phase I (43 in total), plus case studies generated which are (mostly) available on our web site, provide examples of some of the types of projects which will be advanced in phase II E3B (http://community.dur.ac.uk/MiB_NIBB/category/outcomes//).

In common with MiB phase I (where all of the following are evidenced) the major impacts of E3B phase II will be as follows (with a greater emphasis on the earlier listed items):

(i) Products launched (or turnover increased).

(ii) Advancement of Academic-Industry research and development in this arena to higher TRLs.

(iii) Increased sustainability plus improvement to the environment (for example through metal recovery and recycling).

(iv) Jobs created or safeguarded (with a growing fraction outside research and development as projects initiated in phase I advance to higher TRLs and to products).

(v) Industrial-biotechnology based improvement to nutritional health for example through bioprocesses that enrich the provision of iron, zinc and/or vitamin B12.

(vi) Patents awarded.

(vii) New Academic-Industry collaborations instigated (expanding the pool of talent engaged in these sectors).

(viii) Papers published (especially in Discovery Journals).

Projects awarded from flexible funds will require cash and/or in-kind contributions from project partners. A conservative assumption is that matching contributions from Industry will be equivalent to funds awarded (notably in phase I MiB where matching funds were required they did exceed the total amounts awarded) with a 50:50 split between the two categories (cash and in kind). The project partners making these contributions will come from a broad base of current plus newly recruited future members and not solely from the smaller sub-set of partners/participants supporting this application. All network members will be equally eligible for awards under our (robust) governance procedures (for example with no bias to the core sub-set named here).

The E3B management will liaise with members in response to enquiries for expert advice to source the most qualified groups of individuals, and help to compile reports.

E3B will promote engagement (with the public and with stakeholders) to increase awareness of the importance of Metals in Biology and the commercial opportunities that advances in this sub discipline create. CoI Warren has experience in working with broadcasters to produce television programmes (for example). We have also added a Social Scientist with Responsible Research and Innovation (RRI) expertise to the International Advisory Board and will encourage bi-directional flow of information (between researchers and stakeholders including the public). We will also encourage best practice in relation to RRI and Ethical, Legal and Social Aspects of Life Sciences (ELSA) through training events and in grant planning.

The E3B network will expand the pool of talent engaged in research and development related to bioremediation, biomanufacturing and bioenergy production.