Ten Canonical Buildings Pdf _BEST_ Download

Download >>>>> https://shurll.com/2sVEFS

Seminal work for the history of architecture, the authors analyze the Las Vegas' strip to better comprehend the common and ordinary architecture, rather than the iconic buildings proclaimed by modernism | Recommended by Romullo Baratto

For many architects, designing for the senses often means simply designing for sight and touch. This book gives a comprehensive overview of designing for sound, from detailed drawings to texts on the subject. The hope? That better acoustic environments will also mean better buildings | Recommended by Collin Abdallah

This classic examines how architecture defines our understanding of space - and how buildings are sometimes indifferent participants in the urban environment. In Zevi's capable hands the components of architecture come alive, offering an illuminating and provocative perspective on the field of architecture | Recommended by Martita Vial.

You're unlikely to find this book on any typical architecture reading lists, but that doesn't make it any less essential. Robert Bevan guides the reader through the architectural landscape in times of and after a conflict, giving words to what we know but don't often say: that the built environment has cultural and personal significance that stretches far beyond shelter. The leveling of buildings in war is less often the byproduct of hostilities than it is the hostilities themselves. The active and systematic erasure of an urban landscape is the strategic and leveling of identity, culture, and people | Recommended by Katherine Allen

The section is the greatest and most legible tool of architecture - who among us did not grow up entranced by the cut sections of buildings such as the Pantheon or Kowloon Walled City? This book is the grown-up answer to our childhood fascinations, offering detailed drawings of contemporary works. Essays offer invaluable insight into not just the buildings selected but to the idea of the section itself | Recommended by Kaley Overstreet

This book pioneered the concept of townscape. 'Townscape' is the art of giving visual coherence and organization to the jumble of buildings, streets, and space that make up the urban environment | Recommended by Winnie Wu

Humankind relies on specialized metabolites for medicines, flavors, fragrances, and numerous other valuable biomaterials. However, the chemical space occupied by specialized metabolites, and, thus, their application potential, is limited because their biosynthesis is based on only a handful of building blocks. Engineering organisms to synthesize alternative building blocks will bypass this limitation and enable the sustainable production of molecules with non-canonical chemical structures, expanding the possible applications. Herein, we focus on isoprenoids and combine synthetic biology with protein engineering to construct yeast cells that synthesize 10 non-canonical isoprenoid building blocks with 16 carbon atoms. We identify suitable terpene synthases to convert these building blocks into C16 scaffolds and a cytochrome P450 to decorate the terpene scaffolds and produce different oxygenated compounds. Thus, we reconstruct the modular structure of terpene biosynthesis on 16-carbon backbones, synthesizing 28 different non-canonical terpenes, some of which have interesting odorant properties.

As the biosynthesis of isoprenoids is based on the C5 isoprene unit, the different isoprenoid classes differ in their size by five carbon atoms. This creates a stratification in the possible chemical structures and restricts the complexity of isoprenoids to skeletons of 10, 15, 20, or higher multiples of five carbon atoms1. Only very few molecules with a carbon number that deviates from this rule have been identified and, in these rare exceptions, the biosynthetic mechanisms involved are not conserved2,3,4,5,6,7. Thus, the chemical space that lies between the C5-based layers remains largely inaccessible to biological synthesis. Expanding the diversity of isoprenoids by engineering industrial microorganisms, like the yeast Saccharomyces cerevisiae, to produce isoprenoid building blocks with non-canonical sizes would dramatically increase the diversity of these highly valuable molecules and expand their potential industrial applications.

Systematic expansion of the chemical space occupied by biologically-synthesized isoprenoids requires to, first, establish the synthesis of non-canonical isoprenoid building blocks and, subsequently, reconstruct the downstream steps of isoprenoid biosynthesis by identifying or engineering enzymes (terpene synthases, cytochrome P450s, etc.) able to convert the alternative precursors into potentially valuable compounds. Several inspiring chemoenzymatic studies have shown that the substrate promiscuity of terpene synthases can be successfully exploited to synthesize non-canonical terpenoids using alternative, chemically synthesized, substrates8,9,10,11,12,13. Thus, it would be possible to identify or engineer terpene synthases to convert non-canonical substrates. In addition, terpene-oxidizing P450s also display considerable substrate promiscuity14,15,16 and could be exploited to decorate the non-canonical terpene scaffolds produced by such an approach. However, engineering an organism to synthesize an additional class of terpenoids exclusively from sugar also requires establishing biosynthetic pathways for non-canonical prenyl diphosphate substrates that are dedicated to the specific compound group. As the first step in this direction, we achieved the systematic synthesis of C11 terpenes in yeast17. We engineered yeast to produce a precursor with 11 carbon atoms, 2-methyl-GPP, by hijacking a methyltransferase from the cyanobacterial 2-methylisoborneol biosynthesis pathway, which specifically adds a methyl group to GPP, and engineered several monoterpene synthases to preferentially accept 2-methyl-GPP as substrate instead of GPP. As a result, we were able to synthesize several C11 terpene carbon skeletons, establishing proof of concept that it is possible to expand the terpene chemical space by synthetic biology.

Extending this concept to synthesize non-canonical terpenoids with larger size will have considerable impact because structural complexity increases dramatically as the number of carbon atoms increases. Moreover, larger terpenoids, like sesqui- or di-terpenoids, have numerous applications and are frequently used as pharmaceutical agents, fragrances, or high-value chemicals. To identify potentially useful biosynthetic activities that would enable a specific and systematic approach for the biosynthesis of larger terpenoids, we searched for evidence of synthesis of non-canonical terpenes in different organisms. We identified a study reporting the presence of a terpene, named sodorifen, with an unprecedented structure of 16 carbon atoms, dominating the volatile product profile of the rhizobacterium Serratia plymuthica18. The biosynthesis of sodorifen was subsequently reported to involve a methyltransferase (SpSodMT) that catalyzes the sequential methylation and cyclization of FPP to a pentacyclic ring-containing 16-carbon atoms precursor, presodorifenyl diphosphate (PSPP), which is subsequently converted to sodorifen by a terpene synthase (SpSodTPS)19,20. We decided to explore whether SpSodMT could be hijacked for the synthesis of non-canonical isoprenoid building blocks in an engineered microorganism.

In this study, we introduce SpSodMT in yeast and establish robust and orthogonal production of PSPP. We subsequently identify SpSodMT residues responsible for product selectivity and engineer enzyme variants that synthesize nine additional C16 prenyl diphosphate building blocks. By identifying terpene synthases that accept the non-canonical substrates, we utilize this collection of building blocks to produce different terpene scaffolds. Through the identification of one cytochrome P450 enzyme able to decorate the C16 scaffolds, we synthesize several oxygenated non-canonical terpenes. In total, we produce, isolate and structurally characterize 28 isoprenoid compounds with C16 carbon skeletons (Fig. 1). Moreover, we identify several of these compounds to be odor-active.

Having established synthesis of PSPP, we explored the possibility to develop additional non-canonical building blocks in order to create a larger alphabet for re-writing the terpene code. To this end, we examined whether SpSodMT can be engineered to produce different C16 prenyl diphosphates. The mechanism of PSPP synthesis by SpSodMT involves a methyl group addition event leading to the formation of a carbocation, which, in turn, isomerizes to different forms before it is quenched by, possibly, a nearby residue (Fig. 3a and ref. 19). Thus, SpSodMT can be considered as a bifunctional enzyme that combines, in the same active site, the function of a methyltransferase with that of a terpene synthase. We reasoned that it should be feasible to tamper with the terpene synthase reaction to tease out different products. We postulated that if the carbocation cascade that follows the methylation step could be altered by changes in the contour of the active-site pocket or in the physicochemical properties of the residues that line it, then this would result in the synthesis of structurally different prenyl diphosphate products. Thus, we constructed a model of SpSodMT based on the coordinates of the structurally homologous norcoclaurine-6-O-methyltransferase from Thalictrum flavum29 (PDB ID: 5kok) and docked the substrate, FPP, in this model (Fig. 3b). We identified 10 residues (F56, Q57, F58, S190, H191, N219, D272, V273, W276, and L302) that line the FPP binding pocket, and designed rational substitutions in these residues that could derail the carbocation substrate, either by potential stabilization/destabilization of carbocationic intermediates, or by steric interference. In total, we constructed a library of 55 different SpSodMT single-residue variants (Supplementary Data 3). 2b1af7f3a8