CYP105A1 is a well-described cytochrome P450 from Streptomyces griseolus with a broad substrate range. In this work, teams from Saarland University and the University of British Columbia characterized the oxidation of different resin acid diterpenoids. Abietic acid and dehydroabietic acid were selectively hydroxylated resulting in the formation of 15-hydroxyabietic acid and 15-hydroxydehydroabietic acid respectively. In case of isopimaric acid, the enzyme catalyzed the formation of an epoxy group to give the product 15,16-epoxyisopimaric acid. As resin acids and their derivatives exhibit interesting biological properties, and these positions are difficult to address by chemical means, CYP105A1 opens new possibilities for the synthesis of pharmaceutically relevant diterpenoids.

Žáček et al. incubated labial glands of males from two bumblebee species (Bombus terrestris and Bombus lucorum) in vitro with radioactive [1,2-¹⁴C]acetate and deuterated [D₃]acetate to investigate the biosynthesis of sexual pheromones. They found that the labeled substrates are incorporated into various compounds including terpenic alcohols and fatty acids, showing that aliphatic and terpenic pheromone components are synthesized de novo in the labial gland. In their full paper, the authors compare the qPCR analysis of fatty acid synthase transcription levels in fat bodies and labial glands. The results show that the biosynthetic activity is higher for labial gland and a function of the age of B. terrestris males.

Bacteria have developed various strategies for uptake of iron, which is an essential element but poorly bioavailable. Isabelle Schalk highlights a recent study by Raymond et al., who described for the first time a ferricitrate uptake pathway in the Gram-positive bacterium Bacillus cereus. The cytoplasmic membrane of B. cereus carries a siderophore-binding protein, FctC, and an ABC transporter, FctAB. Together, these proteins enable B. cereus to bind both Fe₂Cit₂ and Fe₃Cit₃, making it better able to compete for these essential nutrients.

This issue also contains, among others, notable contributions from Hidde Ploegh (MIT), Herbert Waldmann (Max Planck Institute of Molecular Physiology), and David Sherman (University of Michigan) and Shengying Li (Qingdao Institute of Bioenergy and Bioprocesses). Browse Issue 3/2013 now.

This issue also contains, among others, notable contributions from Christopher Walsh (Harvard Medical School), Barbara Imperiali (MIT) and Karen Allen (Boston University School of Medicine), and Carine Giovannangeli (CNRS, Paris). Browse Issue 17/2012 now.

Also in this issue, Thomas Peters (University of Luebeck) highlights work published recently in Angewandte Chemie that shows that recognition of sialyl Lewis X by E-selectin is an entirely entropically driven process. This highly specific, low-affinity interaction is important in the inflammation cascade and the new thermodynamic explanation might aid the rational design of novel drugs.

In a Full Paper, Nigel Scrutton (University of Manchester) and co-workers present the crystal structure of a truncated form of human ecto-5'-nucleotidase (CD73). CD73 is a dimeric protein expressed on the extracellular side of the plasma membrane and catalyzes the hydrolysis of nucleotide monophosphates, especially AMP. The important role of this enzyme, in regulating adenosine levels, makes it a potential drug target. The crystal structure of this truncated, but still active form will lend valuable structural information to further studies of this important enzyme.

In a Communication, Milan Mrksich (Northwestern University) and co-workers introduce a step-wise synthesis of megamolecules with a precisely defined structure and molecular weights near 300 kDa. They created a fusion protein that is a combination of a cutinase and a haloalkane dehalogenase (HaloTag). This protein was blocked either at the cutinase or at the HaloTag domain and then reacted with a bifunctional linker that enables the covalent reaction with another fusion protein. The bis-(hexa(ethyleneglycol)) linker contains a p-nitrophenyl phosphonate (cutinase substrate) at one end and a hexyl chloride group (HaloTag substrate) at the other. This oligomerization technique might be useful for the creation of molecules that are too large to be synthesized using traditional chemistry and yet too small to be prepared using microfabrication.

This issue also contains, among others, notable contributions from Bridget Stocker (Malaghan Institute of Medical Research), Piet Herdewijn (KU Leuven), and Isabella Felli and the late Ivano Bertini (University of Florence). Browse Issue 16/2012 now.

Also in this issue, Hiroshi Sugiyama and co-workers review fluorophore conjugates of pyrrole-imidazole-based polyamides. These polyamides, which have been derived from DNA-binding antibiotics, are cell-permeable and bind to DNA with sequence specificity and are able to influence gene expression. This Review provides a clear overview of the fluorophores that have been used in conjugation with these agents and their applications in imaging.

Rapid excretion from the body is a major drawback to the use of the neuraminidase inhibitors zanamivir and oseltamivir against influenza. Chemically programmed antibodies that combine long-lasting bioavailability with the action of an inhibitor are potential alternatives. In their Communication, Carlos Barbas (Scripps, San Diego) and co-workers report a new inhibitor based on zanamivir as the chemical programming agent. Zanamivir was first functionalized with a β-lactam and then linked to the monoclonal antibody 38C2 through amide bond formation between the β-lactam and LysH93 in the antibody binding pocket. The resulting chemically programmed antibody showed a dramatically increased half-life in mice (72 h vs 10 min for zanamivir), while its inhibitory activity is comparable to free zanamivir.

This issue also contains, among others, notable contributions from Taifo Mahmud (Oregon State University), Delin You (Shanghai Jiao Tong University), and Wolf-Dieter Fessner (Technical University Darmstadt).Browse Issue 15/2012 now.

Also in this issue, Wymann and Schultz discuss the chemical biology of phosphoinositide 3-kinases (PI3Ks). PI3Ks act as vital parts of the convoluted signaling network that controls cellular processes and hence are targets for drug development and cell biology studies. In this Review, efforts to understand these networks using inhibitors and other small-molecule probes of PI3Ks are described. Chemical and biological methods for the detection and manipulation of phosphoinositide levels inside cells are also discussed. These include the synthesis of cell-permeable and photoactivated phosphoinositide derivatives, and genetically encoded activity and translocation FRET probes.

In a Communication, Kawakami et al. report a new method for the reconstitution of heme-containing proteins with nonnatural metals. In one step, addition of Mn-bound porphyrin prior to sonication of the expression host afforded a modified cytochrome P450 with Mn replacing the natural Fe. This method also yielded Ru- and Mn-containing versions of the heme nitric oxide/oxygen-binding domain. This simple method may allow the design of artificial metalloproteins carrying nonnatural metal centres to achieve novel activity.

Site-selective protein labeling is an example of an important and highly competitive area in which chemistry can contribute to life science research. Recently, Cu-free click chemistry between fluorophores and genetically encoded unnatural amino acids (UAAs) has emerged as an alternative to GFP fusions for imaging of proteins in living cells. In a Full Paper, Borrmann et al. describe the latest UAA based on a bicyclo[6.1.0]nonyne moiety that reacts rapidly with both azide- (strain-promoted azide-alkyne cycloaddition) and tetrazine- (strain-promoted inverse electron-demand Diels–Alder reaction) conjugated dyes inside mammalian cells.

This issue contains other notable contributions from Joshua Maurer (Washington University in St. Louis), Philip Cole (Johns Hopkins University School of Medicine), and Harald Schwalbe (Goethe University Frankfurt).Browse Issue 14/2012 now.