Biocatalysis has widened its scope and relevance since new molecular tools, including improved expression systems for proteins, protein and metabolic engineering, and rational techniques for immobilization, have become available. However, applications are still sometimes hampered by low productivity and difficulties in scaling up. A practical and reasonable step to improve the performances of biocatalysts (including both enzymes and whole-cell systems) is to use them in flow reactors. This review describes the state of the art on the design and use of biocatalysis in flow reactors. The encouraging successes of this enabling technology are critically discussed, highlighting new opportunities, problems to be solved and technological advances.

Proton magnetic resonance imaging (MRI) has recently emerged as a clinical tool to image the lungs. This paper outlines the current technical aspects of MRI pulse sequences, radiofrequency (RF) coils and MRI system requirements needed for imaging the pulmonary parenchyma and vasculature. Lung MRI techniques are presented as a “technical toolkit”, from which MR protocols will be composed in the subsequent papers for comprehensive imaging of lung disease and function (parts 2 and 3). This paper is pitched at MR scientists, technicians and radiologists who are interested in understanding and establishing lung MRI methods. Images from a 1.5 T scanner are used for illustration of the sequences and methods that are highlighted.Main Messages• Outline of the hardware and pulse sequence requirements for proton lung MRI• Overview of pulse sequences for lung parenchyma, vascular and functional imaging with protons• Demonstration of the pulse-sequence building blocks for clinical lung MRI protocols

The continuous flow synthesis of a series of amines was successfully achieved by exploiting the enhanced stability and broad substrate scope of an immobilised transaminase from Halomonas elongata (HEWT).

BackgroundMRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women.MethodsProvided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value.ResultsIn interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a “buffet” of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice.ConclusionNew developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed.Main Messages• MRI evolves as a third lung imaging modality, combining morphological and functional information.• It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients.• In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT.• In interstitial lung disease, it serves for research, but the clinical value remains to be proven.• New users are advised to make themselves familiar with the particular advantages and limitations.

T he development of efficient syntheses for enantiomerically enriched R-hydroxy ketones is an important research focus in the pharmaceutical industry. For example, R-hydroxy ketones are found in antidepressants, in selective inhibitors of amyloid-β protein production (used in the treatment of Alzheimer's), in farnesyl transferase inhibitors (Kurasoin A and B), and in antitumor antibiotics (Olivomycin A and Chromomycin A3). Moreover, R-hydroxy ketones are of particular value as fine chemicals because of their utility as building blocks for the production of larger molecules. They can also be used in preparing many other important structures, such as amino alcohols, diols, and so forth. Several purely chemical synthetic approaches have been proposed to afford these compounds, together with some organocatalytic strategies (thiazolium-based carboligations, proline R-hydroxylations, and so forth). However, many of these chemical approaches are not straightforward, lack selectivity, or are economically unattractive because of the large number of chemical steps required (usually combined with low enantioselectivities).In this Account, we describe three different biocatalytic approaches that have been developed to efficiently produce R-hydroxy ketones:(i) The use of thiamine diphosphate-dependent lyases (ThDP-lyases) to catalyze the umpolung carboligation of aldehydes. Enantiopure R-hydroxy ketones are formed from inexpensive aldehydes with this method. Some lyases with a broad substrate spectrum have been successfully characterized. Furthermore, the use of biphasic media with recombinant whole cells overexpressing lyases leads to productivities of ∼80-100 g/L with high enantiomeric excesses (up to >99%).(ii) The use of hydrolases to produce R-hydroxy ketones by means of (in situ) dynamic kinetic resolutions (DKRs). Lipases are able to successfully resolve racemates, and many outstanding examples have been reported. However, this approach leads to a maximum theoretical yield of 50%. As a means of overcoming this problem, these traditional lipase-catalyzed kinetic resolutions are combined with racemization of remnant substrate, which can be done in situ or in separate compartments. Examples showing high conversions (>90%) and enantiomeric excesses (>99%) are described.(iii) Whole-cell redox processes, catalyzed by several microorganisms, either by means of free enzymes (applying a cofactor regeneration system) or by whole cells. Through the use of redox machineries, different strategies can lead to high yields and enantiomeric excesses. Some enantiopure R-hydroxy ketones can be formed by reductions of diketones and by selective oxidations of vicinal diols. Likewise, some redox processes involving sugar chemistry (involving R-hydroxy ketones) have been developed on the industrial scale. Finally, the redox whole-cell concept allows racemizations (and deracemizations) as well.These three strategies provide a useful and environmentally friendly synthetic toolbox. Likewise, the field represents an illustrative example of how b...