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Sub-series 10: Australian Gas Light Company industrial relations records, 1896-1975

Series 03: Negatives of trams, trains, railways and model railways in N.S.W. and Australia, ca. 1920-1970 / chiefly photographed by Len A. Clark

Nature programs the structural folding of an enzyme that allows its on-demand biofunctionality; however, it is still a long-standing challenge to manually modulate an enzyme’s conformation. Here, we design an exogenous hydrogen-bonded organic framework to modulate the conformation of cytochrome c, and hence allow non-native bioactivity for the enzyme. The rigid hydrogen-bonded organic framework, with net-arranged carboxylate inner cage, is in situ installed onto the native cytochrome c. The resultant hydrogen-bonded nano-biointerface changes the conformation to a previously not achieved catalase-like species within the reported cytochrome c-porous organic framework systems. In addition, the preserved hydrogen-bonded organic framework can stabilize the encapsulated enzyme and its channel-like pores also guarantee the free entrance of catalytic substrates. This work describes a conceptual nanotechnology for manoeuvring the flexible conformations of an enzyme, and also highlights the advantages of artificial hydrogen-bonded scaffolds to modulate enzyme activity.
Heme units are immobilised in diverse heme enzymes for oxidation, and have been immobilised also in hydrogen-bonded organic frameworks. Here, the authors show the use of hydrogen-bonded organic framework to modulate the enzyme’s conformation and show different biofunction from the original.

Nature communications, 2022-08, Vol.13 (1), p.4816-4816, Article 4816

Hydrogen-bonded organic framework biomimetic entrapment allowing non-native biocatalytic activity in enzyme

The pharmaceutical industry, driven by an increasing need to deliver new and more effective medicines to patients, is increasingly turning to the use of engineered biocatalysts for both lead generation of active compounds and the sustainable manufacture of active pharmaceutical ingredients. Advances in enzyme discovery, high-throughput screening and protein engineering have substantially expanded the available biocatalysts, and consequently, many more synthetic transformations are now possible. Enzymes can be fine-tuned for practical applications with greater speed and likelihood of success than before, thereby leading to greater predictability and confidence when scaling up these processes. Coupled with a greater awareness of which reactions are suitable for biocatalysis (for example, biocatalytic retrosynthesis), new chemoenzymatic and multi-enzyme processes have been designed and applied to the synthesis of a range of important pharmaceutical target molecules. Increasingly, researchers are exploring opportunities for using immobilized biocatalysts in flow conditions. In this Review, we discuss some of the key drivers and scientific developments that are expanding the application of biocatalysis in the pharmaceutical industry and highlight potential future developments that likely will continue to increase the impact of biocatalysis in drug development.
Engineered biocatalysts are increasingly being used for both the identification and manufacture of active pharmaceutical ingredients. Here, the authors review key developments that are expanding the use of biocatalysis in the pharmaceutical industry.

Nature reviews. Chemistry, 2018-12, Vol.2 (12), p.409-421

Extending the application of biocatalysis to meet the challenges of drug development

Squalene-hopene cyclases are a highly valuable and attractive class of membrane-bound enzymes as sustainable biotechnological tools to produce aromas and bioactive compounds at industrial scale. However, their application as whole-cell biocatalysts suffer from the outer cell membrane acting as a diffusion barrier for the highly hydrophobic substrate/product, while the use of purified enzymes leads to dramatic loss of stability. Here we present an unexplored strategy for biocatalysis: the application of squalene-hopene-cyclase spheroplasts. By removing the outer cell membrane, we produce stable and substrate-accessible biocatalysts. These spheroplasts exhibit up to 100-fold higher activity than their whole-cell counterparts for the biotransformations of squalene, geranyl acetone, farnesol, and farnesyl acetone. Their catalytic ability is also higher than the purified enzyme for all high molecular weight terpenes. In addition, we introduce a concept for the carrier-free immobilization of spheroplasts via crosslinking, crosslinked spheroplasts. The crosslinked spheroplasts maintain the same catalytic activity of the spheroplasts, offering additional advantages such as recycling and reuse. These timely solutions contribute not only to harness the catalytic potential of the squalene-hopene cyclases, but also to make biocatalytic processes even greener and more cost-efficient.
Squalene-hopene cyclase are membrane-bound enzymes used to produce bioactive compounds at industrial scale. Here, the authors show squalene-hopene cyclase spheroplasts, obtained by removing the outer cell membrane, having a higher catalytic activity than the enzymes and the whole cells, and their cross-linking for recycling and reuse.

Nature communications, 2022-10, Vol.13 (1), p.6269-6269, Article 6269

Spheroplasts preparation boosts the catalytic potential of a squalene-hopene cyclase

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Sub-series 10: Australian Gas Light Company industrial relations records, 1896-1975

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Series 03: Negatives of trams, trains, railways and model railways in N.S.W. and Australia, ca. 1920-1970 / chiefly photographed by Len A. Clark

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Hydrogen-bonded organic framework biomimetic entrapment allowing non-native biocatalytic activity in enzyme

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Extending the application of biocatalysis to meet the challenges of drug development

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Spheroplasts preparation boosts the catalytic potential of a squalene-hopene cyclase

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