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.

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.

Oils and fats of vegetable and animal origin have been the most important renewable feedstock of the chemical industry in the past and in the present. A tremendous geographical and feedstock shift of oleochemical production has taken place from North America and Europe to southeast Asia and from tallow to palm oil. It will be important to introduce and to cultivate more and new oil plants containing fatty acids with interesting and desired properties for chemical utilization while simultaneously increasing the agricultural biodiversity. The problem of the industrial utilization of food plant oils has become more urgent with the development of the global biodiesel production. The remarkable advances made during the last decade in organic synthesis, catalysis, and biotechnology using plant oils and the basic oleochemicals derived from them will be reported, including, for example, ω-functionalization of fatty acids containing internal double bonds, application of the olefin metathesis reaction, and de novo synthesis of fatty acids from abundantly available renewable carbon sources.

Esterases (EC 3.1.1.x) represent a diverse group of hydrolases catalyzing the cleavage and formation of ester bonds and are widely distributed in animals, plants and microorganisms. Beside lipases, a considerable number of microbial carboxyl esterases have also been discovered and overexpressed. This review summarizes their properties and classification. Special emphasis is given on their application in organic synthesis for the resolution of racemates and prostereogenic compounds. In addition, recent results for altering their properties by directed evolution are presented.

N ature has evolved highly efficient systems in the form of cascade reactions, which assemble the metabolic networks that support life (growth and survival). The basic principle of cascade reactions is also frequently used in biocatalysis, using enzymes in isolation, as well as in combination with chemocatalysts (see Fig. 1 and Box 1 for definition of terms) [1][2][3][4][5][6][7] . As there is no need for purification and isolation of intermediates, operating time, production costs and waste are reduced, and concomitantly, overall yields are improved. In addition, the problem of unstable or difficult to handle intermediates can be overcome, and reactivity as well as selectivity can be enhanced by avoiding unfavourable reaction equilibria through the cooperative effects of multiple catalysts 8 . Starting in the 1980s, the early examples of the combination of chemo-and biocatalysts were reported by the van Bekkum group, who pioneered the development of a process to make the sugar substitute d-mannitol from readily available d-glucose through the combination of a heterogeneous metal-catalysed hydrogenation and an enzyme-catalysed isomerization 9 . The first broadly applied technology for the combination of enzyme and metalcatalysts, which was the research subject of many academic groups as well as industry, emerged in the 1990s from the Williams group 10,11 and aimed to achieve higher yields than classical kinetic resolution of racemates, thus overcoming the limitation of a maximum yield of 50% in the latter case. A prominent example of work that developed this theme is the combination of lipase-catalysed kinetic resolution via acylation of secondary alcohols with Pd-or Rh-catalysed racemization via reversible transfer hydrogenation to achieve a dynamic kinetic resolution (DKR) [12][13][14] . This example was facilitated in part because lipases are active and stable in organic solvents. Later, for instance, Turner's group combined a monoamine oxidase-catalysed imine formation with a chemical reduction 15 to achieve the 100% theoretical yield through a deracemization process. In addition to the combination of metalcatalysis with enzymes, organocatalysis, electrochemistry and light-induced reaction couples have since then been studied extensively, going far beyond the scope of a DKR.The challenges to combining chemo-and biocatalysis in cascades (see Box 1 for definitions and Table 1) can be daunting, not least the requirement for the chemical step to occur in the presence of water, the preferred solvent for enzymes 3 . This Review therefore highlights recent examples of the combination of chemo-and biocatalysts in aqueous multistep syntheses, and looks at how to overcome limitations by, for example, design of appropriate reaction conditions, protein engineering and advanced reactor concepts. Furthermore, trends such as the integration of transition metalcatalysis into microorganisms and the introduction of novel chemistry into engineered enzymes are discussed, and a critical assessment of the impact of this research ...