A growing global population and rising living standards inevitably enforce the conflict between satisfying the people's demands for goods and services, on one hand, and the sustainable development requirements and the considerate treatment of nature and earth's resources, on the other. It is not only that fossil carbon sources will become limited in the future, but there is also a growing pressure to renounce the exploitation of currently treated and prospected sites for environmental reasons. Accidents, such as the recent oil disaster in the Gulf of Mexico, motivate this tendency even more. To stop the rigorous and reckless exploitation of the earth's resources, alternative resources must be recovered, and clean techniques have to be developed, offered, and applied. The turnaround in thinking and acting has been already evident in recent times, mostly with respect to energy production, for which sustainable resources and clean techniques are increasingly implemented to substitute today's oil and coal-based production .
Likewise to the issue of clean energy production, a change is necessary in the societies' approach of how to improve the future production of commodities [2–4]. Thereby, industrial (white/green) biotechnology offers an elegant way to provide alternatives [5–7] via the application of microorganisms or components of cells in combination with a broad spectrum of new-generation renewable substrates.
Applying biotechnological processes, the chemical industry has for ages produced, for instance, alcohols and organic acids mainly to be employed as chemicals, but above all as energy carriers in bulk quantities. Of those, bioethanol [8–11] is a recent example of modern fuels for motor vehicles , while biobutanol is expected to be another one [13, 14]. Based on this knowledge of how to produce bulk-scale energy carriers, recent intentions envisage the extension of platform chemicals for wider applications [13, 15–18]. Special attempts are directed towards the synthesis of chemicals, such as 1,3-propanediol , succinate , gluconic acid [21–23], or citric acid . Likewise, 2-hydroxyisobutyric acid (2-HIB) fits well into this scheme as it is gaining importance as a platform chemical. In particular, it can be used as a precursor for methacrylic acid [15, 25], a monomeric compound required for the synthesis of such prominent products like Plexiglas® (Evonik Röhm GmbH, Essen, Germany) and as an important ingredient for coating materials, paint, and glues.
In general, traditional biotechnological processes, such as those for bioethanol production, are based on carbon sources of the so-called first generation, i.e., carbohydrates such as sugars or starches directly derived from plants . Nowadays, the focus has shifted to second-generation feed stocks [11, 27], which rely on complex plant materials, such as cellulose, hemicellulose, and lignin; the monomers of which are, however, more difficult to access , especially in terms of biosynthesis. Additionally, the concept of using arable land to grow plants solely as substrate resources for biotechnological processes is a matter of controversial debate, not only in view of substituting natural biotopes (e.g., rain forests) by monocultures , but also in view of reasonable conflicts with nutritional issues and the food production industry [30, 31].
One solution and actual expectation in terms of a future sustainable bulk chemical production is the utilization of substrates of the third generation, i.e., diverse gas mixtures which deliver carbon as well as reducing power from different sources [4, 32, 33]. This implies the utilization of CO2 as a carbon source since CO2 accumulates as a waste product of energy production from fossil resources. At the same time, the resulting consumption of CO2 within such a new production scheme also provides a fundamental argument to support processes that counteract climate change [13, 34]. The required reducing power might be delivered by hydrogen generated, e.g., by solar energy  or wind power . Some perspectives of how to use CO2, not only as a substrate for diverse syntheses, but also for various biosyntheses, have recently been presented at the Dechema colloquium[37, 38]. Among others, the processes developed by Coskata Inc., Illinois, USA, employing a variety of materials which can be converted into renewable fuels and chemicals by biofermentation of synthesis gas, have been demonstrated. Also, the development of special designer bugs, being capable of using flue gas as a substrate, has been introduced at the colloquium Sustainable Bioeconomy. However, the biggest challenge of those miscellaneous approaches is and will be the competition with the established processes and the implemented production schemes of the chemical industry [3, 31, 40], where the biobased synthesis is often still defeated. Nevertheless, in this investigation, another perspective of how to use CO2 to sustainably produce 2-HIB as a building block is presented.
We recently discovered a novel enzyme, the 2-HIB-coenzyme A mutase, which proves to be an ideal catalyst for the production of 2-HIB, especially, given that 2-HIB synthesis with this enzyme only requires a one-step isomerization of metabolites that are essential for the metabolism of a wide range of bacteria, i.e., 3-hydroxybutyryl-coenzyme A (3-HB-CoA) [25, 41–44]. The synthesis of 2-HIB and its excretion into the cultivation broth can be realized by employing strains that express this heterologous enzyme in combination with an existing overflow carbon metabolism. The selection of suitable strains thus allows different substrates for the production of 2-HIB to be utilized, as has been demonstrated by using fructose , D Przybylski, unpublished work]. However, in seeking sustainability, the application of fructose, a substrate of the first generation, will not meet the requirements to qualify carbohydrates as future substrates.
Therefore, we have applied the 2-HIB-coenzyme A mutase to demonstrate the sustainable and clean production of 2-HIB from carbon dioxide and hydrogen by exploiting the chemo-litho-autotrophic metabolism of the knallgas bacterium Cupriavidus necator (Alcaligenes eutrophus) H16 PHB−4 [46, 47]. The synthesis of 2-HIB was successful at the experimental proof of principle stage. Model data were added to confirm the metabolic potential of such a process.