The diversity of small molecules formed via plant diterpene metabolism offers a rich source of known and potentially new biopharmaceuticals. Among these, the microtubule-destabilizing activity of pseudolaric acid B (PAB) holds promise for new anticancer agents. PAB is found, perhaps uniquely, in the coniferous tree golden larch (Pseudolarix amabilis, Pxa). Here we describe the discovery and mechanistic analysis of golden larch terpene synthase 8 (PxaTPS8), an unusual diterpene synthase (diTPS) that catalyzes the first committed step in PAB biosynthesis. Mining of the golden larch root transcriptome revealed a large TPS family, including the monofunctional class I diTPS PxaTPS8, which converts geranylgeranyl diphosphate into a previously unknown 5,7-fused bicyclic diterpene, coined "pseudolaratriene." Combined NMR and quantum chemical analysis verified the structure of pseudolaratriene, and co-occurrence with PxaTPS8 and PAB in P. amabilis tissues supports the intermediacy of pseudolaratriene in PAB metabolism. Although PxaTPS8 adopts the typical three-domain structure of diTPSs, sequence phylogeny places the enzyme with two-domain TPSs of mono-and sesqui-terpene biosynthesis. Site-directed mutagenesis of PxaTPS8 revealed several catalytic residues that, together with quantum chemical calculations, suggested a substantial divergence of PxaTPS8 from other TPSs leading to a distinct carbocation-driven reaction mechanism en route to the 5,7-trans-fused bicyclic pseudolaratriene scaffold. PxaTPS8 expression in microbial and plant hosts provided proof of concept for metabolic engineering of pseudolaratriene. diterpene biosynthesis | Pseudolarix amabilis | plant natural products | pseudolaric acid | chemotherapeutic drug

Self-assembled monolayers (SAMs) have been widely studied as potential lubricants for microelectromechanical system (MEMS) devices. However, these single-layer films have nominally been found to be insufficient for mitigating wear in sliding contacts because of their rapid breakdown under the high pressures found within the nanoasperity junctions at such interfaces. As such, there is a critical need to explore approaches beyond simple, single-component SAMs toward films that introduce additional lubricant molecules into the system. Because alcohol vapors have previously been shown to reduce wear in MEMS devices, here we have investigated a mixed monolayer consisting of an octadecyltrichlorosilane (OTS) SAM infused with 3-phenyl-1-propanol (3P1P), assembled on silica nanoparticle films. A combination of atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), thermal gravimetric analysis (TGA), and FTIR spectroscopy was employed to investigate the structural and frictional properties of the mixed monolayers and to evaluate surface wear as a function of time. The nanoparticle film/AFM tip junction provides a ready mimic for the asperity-asperity contacts found in MEMS devices. Here it was found that for a mixed monolayer of OTS with ca. 15% 3P1P, the surfaces showed dramatically reduced friction and no wear under the same load conditions as surfaces with an OTS SAM alone. Moreover, the multicomponent film also displayed no increase in friction and exhibited no wear even after 14 h of shearing contact in an AFM at loads that would break down the OTS layer. The ability of the OTS SAM to trap short-chain alcohols, such as 3P1P, and to release them under load suggests a simple MEMS lubrication scheme that could be readily integrated into MEMS device architectures.

We report the first theoretical study of noncovalent and covalent interactions in formic acid (FA)-SO(2) complexes. Using ab initio and DFT model chemistries, five stable noncovalent complexes were identified, as well as a covalent adduct, formic sulfurous anhydride HOSO(2)CHO. syn-FA is predicted to form two nonplanar bidentate complexes with SO(2): the more stable one contains a normal hydrogen bond donated by OH, and the less stable one contains a blue-shifted hydrogen bond donated by CH. Both are stabilized by charge transfer from FA to SO(2). anti-FA forms three planar complexes of nearly equal energy containing OH-to-SO(2) hydrogen bonds. Formic sulfurous anhydride forms via an endothermic concerted cycloaddition. Natural bond orbital analysis showed that the bidentate SO(2)-FA complexes are stabilized by n → π* donation from FA to SO(2), and back-donation from SO(2) n and π* orbitals into FA σ(OH)* or σ(CH)* orbitals. The bidentate formic acid-SO(2) complex that contains an O-H···O hydrogen bond is more stable than the similar nitric acid-SO(2) complex. The latter contains a stronger hydrogen bond but shows no O→S charge transfer interaction.

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