**Preface to "Biocatalytic Synthesis of Bioactive Compounds"**

Biocatalysis, the application of enzymes as catalysts for chemical synthesis, has become an increasingly valuable tool for the synthetic chemist. Enzymatic transformations carried out by partially purified e nzymes o r w hole-cell c atalysts a re u sed f or t he p roduction o f a w ide variety of compounds ranging from bulk to fine c hemicals. I n t he fi eld of fin e che micals, the main application clearly lies in the exploitation of the outstanding properties of these biocatalysts with respect to chemoselectivity, regioselectivity, and especially stereoselectivity in the production of enantiomerically pure compounds. Until recently, chemical development companies regarded biocatalysis as a method to be attempted only when all other chemical options failed. Currently, there are clear signs that this view is changing radically, with many of the new process developments revealing the benefits to be gained by using biocatalysis on a commercial scale. Biocatalytic processes have a number of advantages over the corresponding chemical methods. The conditions for such processes are mild and, in the majority of cases, do not require the protection of other functional groups. Moreover, eliminating the need for several chemical synthetic steps has had a dramatic impact on the overall economics. In many cases, biological methods are also enantiospecific, allowing for the production of chiral products from racemic mixtures. Furthermore, the features governing their regiospecificity d iffer f rom t hose c ontrolling c hemical s pecificity an d, in deed, it is possible to obtain biotransformations at centers that are chemically unreactive. Economically, biocatalytic processes are often cheaper and more direct than their chemical counterparts, and the conversions normally proceed under conditions that are regarded as ecologically acceptable.

The aim of this Special Issue is to present studies focused on biocatalysis as applied to the organic synthesis of bioactive compounds and their precursors. The obtained contributions deal with biotransformations, including the stereoselective synthesis of bioactive chemical compounds, active pharmaceutical ingredients, and natural products. The production of interesting bioactive compounds is covered in the eight articles comprising seven research articles and a review.

Two of these papers deal with fungal metabolism and fungi-mediated biotransformations. The first paper deals with improving β-pinene bioconversion by mutagenesis and adaptation of the fungus *Chrysosporium pannorum* A-1. A second paper describes a study on the biotransformation of bioactive coumarins by filamentous fungi.

On the other hand, the conversion of oleic acid into azelaic and pelargonic acid by a chemoenzymatic route represents a sustainable alternative to ozonolysis, currently employed at the industrial scale to perform the reaction. In addition, the findings on a gram-scale limonene production process using engineered Escherichia coli provide a basis for the development of an economic and industrially relevant bioprocess.

Alkene cleavage is a possibility to generate aldehydes with olfactory properties for the fragrance and flavor i ndustry. A dye-decolorizing peroxidase (DyP) o f the basidiomycete *Pleurotus sapidus* is the first described DyP with alkene cleavage activity towards aryl alkenes and showed potential as biocatalyst for flavor production.

Isoflavones in soybeans are well-known p hytoestrogens. Soy isoflavones present in conjugated forms are converted to aglycone forms during processing and storage. Isoflavone aglycones (IFAs) of soybeans in human diets have poor solubility in water, resulting in low bioavailability and bioactivity. Enzyme-mediated glycosylation is an efficient a nd e nvironmentally f riendly w ay to

modify the physicochemical properties of soy IFAs. Thus, Jung et al. studied the enrichment of polyglucosylated isoflavones from soybean isoflavone aglycones using optimized amylosucrase transglycosylation. In the same line, Chang et al. studied the potential industrial production of a well-soluble, alkaline-stable, and anti-inflammatory isoflavone glucoside from 8-hydroxydaidzein glucosylated by recombinant amylosucrase of *Deinococcus geothermalis*.

Finally, the review discusses the use of halogenating enzymes in fine chemical syntheses, detailing the many steps that are still needed before halogenating enzymes are considered reliable, flexible, and sustainable catalysts for halogenation.

Overall, these eight contributions provide the reader with relevant fresh insights into the use of enzymes and whole cells as biocatalysts.

> **Josefina Aleu** *Editor*

*Article*
