Understanding the BASEs for catalysis in class II diterpene cyclases results in novel product chemistries

Labdane-related diterpenoids are a large group of natural products (over 7,000 known) with applications in many industries. The cyclization of the general diterpene precursor, (E,E,E)-geranylgeranyl diphosphate, into various bicyclic diterpene precursors catalyzed by class II diterpene cyclases characterizes labdane-related diterpenoid biosynthesis. The catalytic acid in the protonation-initiated cyclization reaction has been previously identified, however the catalytic base was not known. Using ent-copalyl diphosphate synthase from Arabidopsis thaliana, involved in gibberellin phytohormone biosynthesis, site-directed mutagenesis studies have uncovered the catalytic base responsible for deprotonation, which consists of a water molecule ligated, in part, by the side-chains from a highly conserved His and Asn dyad. Substitution of smaller side chains for either of these residues leads to addition of water, resulting in production of the hydroxylated variant of ent-copalyl diphosphate, ent-copal-8-ol diphosphate. Whereas, substitution of aromatic residues for the His blocks water access, and stabilizes the carbocation intermediate, thereby facilitating rearrangement around the initially formed hydrocarbon bicycle, resulting in formation of (-)-kolavenyl diphosphate. These mutants provide insights into class II diterpene cyclase catalysis, represent novel enzymatic activities and illustrate how the plasticity of class II diterpene cyclases underlies the observed diversity of labdane-related diterpenoids, thus, uncovering the BASEs for catalysis

Building material capabilities: A socio-technical analysis of composite product development and manufacturing strategy

The development of advanced material requires much more than purely technical knowledge. This paper presents a socio-technical analysis of industrial capability issues for composites material product. The central idea behind this work is to provide a framework to identify and examine important growth drivers in composites. Composites are engineered materials, made from a combination of constituent materials with different properties, and find applications in a variety of business sectors and contribute towards a sustainable economy. The main goal of this paper is to shed some light on how the composites industry could accelerate production rates, meet demands for sophisticated products in high volumes and reach advanced levels of industrialisation

From composite material technologies to composite products: A cross-sectorial reflection on technology transitions and production capability

Materials, since the dawn of time, have played a crucial role in the development of civilization. Pre-history ages are fundamentally characterized by the material humans mastered, while the transitions to new materials have always marked a different socio-technical order. In this work we are going to investigate a relatively new material class, composites, in order to explain the issues the industry is currently facing. We are going to discuss material in the context of developing products that take full advantage of the benefits that composites can offer. The main idea behind this work is to understand how composite material technologies create growth and how the properties of those materials influence production capability and manufacturability. This work is the result of the EPSRC Centre for Innovative Manufacturing in Composites Platform research in the UK. It started with the bold intention to go beyond conventional research in composite material and explore the mechanisms of industrial change and growth through material. An examination of cases from a diverse range of sectors, acted as a platform to initiate a conversation on the issues practitioners are facing when adapting their products, or processes, to composite technologies, or when moving from a craftsman approach to state-of-theart material and process technologies. This paper presents insights from a sector/market agnostic point of view to probe the socio-technical considerations related to the diffusion of manufacturing innovation concerning composites and their production capabilities.The paper makes three main contributions. First, it presents a discussion on the capability issues regarding composites. Second, it presents empirical evidence on industrializing in composite material technologies. Finally, building on empirical evidence and previous literature, it describes the feedback loops during the composite product development process. The paper concludes with a reflection on current theories of innovation management on composite material technologies