Over the past ten years, scientific and technological advances have established biocatalysis as a practical and environmentally friendly alternative to traditional metallo- and organocatalysis in chemical synthesis, both in the laboratory and on an industrial scale. Key advances in DNA sequencing and gene synthesis are at the base of tremendous progress in tailoring biocatalysts by protein engineering and design, and the ability to reorganize enzymes into new biosynthetic pathways. To highlight these achievements, here we discuss applications of protein-engineered biocatalysts ranging from commodity chemicals to advanced pharmaceutical intermediates that use enzyme catalysis as a key step.
Pharmaceutical synthesis can benefit greatly from the selectivity gains associated with enzymatic catalysis. Here, we report an efficient biocatalytic process to replace a recently implemented rhodium-catalyzed asymmetric enamine hydrogenation for the large-scale manufacture of the antidiabetic compound sitagliptin. Starting from an enzyme that had the catalytic machinery to perform the desired chemistry but lacked any activity toward the prositagliptin ketone, we applied a substrate walking, modeling, and mutation approach to create a transaminase with marginal activity for the synthesis of the chiral amine; this variant was then further engineered via directed evolution for practical application in a manufacturing setting. The resultant biocatalysts showed broad applicability toward the synthesis of chiral amines that previously were accessible only via resolution. This work underscores the maturation of biocatalysis to enable efficient, economical, and environmentally benign processes for the manufacture of pharmaceuticals.
in 2007, followed by postdoctoral studies at York University (UK) and Greifswald University (Germany). In 2010, she transitionedto industry applying and developing biocatalytic technologies at Novacta in the UK, prior to joining Chemical Process Development at GSK, with responsibility for the development and implementation of new biocatalytic technologyi nboth pre-and post-commercialization routes. Since Dec. 2016, Radka is leading the Bioreactions group in GDC at the Novartis Institute for Biomedical Research in Basel, Switzerland. Jeffrey Moore obtained his PhD in Chemical Engineeringf rom the California Institute of Technology in 1996 as Frances Arnold's first Directed Evolution graduate student. His foundational work led to an evolved p-nitrobenzyl esterase and the Lonza Centenary Prize (1997). In 1996, he joined the Biocatalysis Group of Merck & Co.in Rahway NJ, spending two decades inventing new enzymes and new enzymatic processes. In 2018, he transitionedtothe Merck Protein EngineeringG roup responsible for evolving enzymes for the discovery,d evelopmenta nd commercials cale manufacture of medicines. He has been awarded aUS Presidential Green Chemistry Award (2010), the BioCat2012 Award (2012) and the Thomas Edison Inventorship Award (2014). Kai Baldenius studied chemistry in Hamburg and Southampton. He received his PhD for research in asymmetric organometallic catalysis, supervised by H. tom Dieck and H. B. Kagan. After his postdoc on natural product synthesis with K. C. Nicolaou at the Scripps Research Institute he joined BASF in 1993. Kai served BASF in various functions (R&D, production, marketing, sales) before he took the lead of BASF'sbiocatalysis research for almost ad efcade. He left BASF to become afree-lancing consultanti n2019 and in 2020 he has founded Baldenius Biotech Consulting. Uwe T. Bornscheuer studied chemistry and received his PhD in 1993 at Hannover University followed by apostdoc at Nagoya University (Japan). In 1998, he completed his Habilitation at Stuttgart University about the use of lipases and esterasesi n organic synthesis. He has been Professor at the Institute of Biochemistry at Greifswald University since 1999. Beside other awards, he received in 2008 the BioCat2008 Award. He was just recognized as "Chemistry Europe Fellow". His current research interest focuses on the discovery and engineering of enzymes from various classes for applications in organic synthesis, lipid modification, degradation of plastics or complex marine polysaccharides.
Enzyme-catalyzed reactions have begun to transform pharmaceutical manufacturing, offering levels of selectivity and tunability that can dramatically improve chemical synthesis. Combining enzymatic reactions into multistep biocatalytic cascades brings additional benefits. Cascades avoid the waste generated by purification of intermediates. They also allow reactions to be linked together to overcome an unfavorable equilibrium or avoid the accumulation of unstable or inhibitory intermediates. We report an in vitro biocatalytic cascade synthesis of the investigational HIV treatment islatravir. Five enzymes were engineered through directed evolution to act on non-natural substrates. These were combined with four auxiliary enzymes to construct islatravir from simple building blocks in a three-step biocatalytic cascade. The overall synthesis requires fewer than half the number of steps of the previously reported routes.
Consumers' desires to either reduce the risk of or manage a specific health condition through improved diet have stimulated the research of agricultural products for their potential health beneficial components such as tocopherols and natural antioxidants. Soft wheat is one of the major crops in Maryland, with little information available about its potentially beneficial components. This study examined eight selected Maryland-grown soft wheat varieties or experimental lines for their potential beneficial components including tocopherols, carotenoids, total phenolics and phenolic acids and their antioxidant properties, including Fe(2+) chelating capacity and free radical scavenging activities against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(*) ), radical cation ABTS(*)(+), and oxygen radical (ORAC). The results showed that all tested soft wheat grain samples contained alpha-tocopherol, with a range of 3.4-10.1 microg/g. Lutein was the primary carotenoid present in the grain samples at a level of 0.82-1.14 microg/g, along with significant amounts of zeaxanthin and beta-carotene. Vanillic, syringic, p-coumaric, and ferulic acids were found in soluble free, soluble conjugated, and insoluble bound forms in the grain extracts, with ferulic acid as the predominant phenolic acid. The eight soft wheat varieties differed in their antioxidant properties. The tested wheat grain samples exhibited ED(50) values against DPPH(*) of 23-27 mg of grain equiv/mL, ORAC of 32.9-48 micromol of Trolox equiv (TE)/g, and ABTS(*)(+) scavenging capacity of 14.3-17.6 micromol of TE/g. These data suggest the possibility of producing soft wheat varieties rich in selected health beneficial factors for optimum human nutrition though breeding programs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.