The determination of aqueous solubility in a high-throughput screening environment is invaluable in the selection of the most promising potential drug candidates. We describe a fast method based on laser nephelometry that can determine the solubility of potential drug candidates (usually from combinatorial chemistry) supplied as dimethyl sulfoxide (DMSO) solutions in 96-well plates. In the sample, the percent DMSO is kept constant allowing direct comparison of results. The nephelometric method has been shown to produce results equivalent to those produced by an HPLC method and to be largely unaffected by colored solutions.

Transaminases have attracted considerable interest in their use as biocatalysts for the synthesis of compounds containing chiral amine units, which are widespread within the pharmaceutical, agrochemical, and fine chemical industry. Recent developments in enzyme- and process-engineering have expedited their use in asymmetric synthesis; however, industrial applications are still hindered by a number of factors, including equilibrium thermodynamics, product inhibition, and poor substrate tolerance. Detailed and comprehensive approaches to each of these challenges have been reported during the last two decades; the most representative enzyme discovery and screening strategies, protein and equilibrium engineering, and immobilization techniques are reviewed herein. Furthermore, we present a detailed look into the applications of transaminases for the synthesis of a variety of amine-containing compounds and the integration of transaminases into multienzymatic systems that allow access to a variety of highly complex products for the end user.

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Biocatalysis over the past few years has matured into an essential tool for modern, cost effective and sustainable pharmaceutical manufacturing. While some reaction classes are well established, and may even be the option of first intent, other more recently discovered enzyme classes are being rapidly developed both in academia and industry. Notwithstanding this, there are further promising enzymes that require further investment and investigation to allow their future industrial use. We here outline GSK's perspective on the current status of biocatalysis for pharmaceutical manufacturing and provide our views on areas of significant potential.

Massetolides A-H (1-8), novel cyclic depsipeptides, and the known compound viscosin (9) have been isolated from cultures of two Pseudomonas sp. isolated from a marine alga and a marine tube worm, respectively. Massetolide A (1) and viscosin (9) exhibit in vitro antimicrobial activity against Mycobacterium tuberculosis and Mycobacterium avium-intracellulare. Precursor-directed biosynthesis has been used to generate unnatural massetolides 11-13 incorporating nonprotein amino acids.