Flavors and fragrances are organic compounds that interact with our taste and olfactory senses to bring an overall enjoyment of the products (K R et al., 2022, Burger et al., 2019, Braga et al., 2018). Since the introduction of vanillin and coumarin to the market in the 19th century, the global demand for flavors and fragrances has steadily increased, with an expected market value of $30.5 billion by 2024 (Jiang and Wang, 2023). This is driven by the rising demand for consumer products, e.g., food, beverages, personal care, and cosmetics, with enhanced tastes and aromas (K R et al., 2022, Jiang and Wang, 2023). Most flavor and fragrance molecules belong to groups of compounds, including aromatics, alcohols, aldehydes, ketones, fatty acids, esters, pyrazines, terpenes, and lactones (Fig. 1A) (Paulino et al., 2021). Based on the origin, they can be categorized as natural, nature-identical, and artificial ones (Braga et al., 2018). Natural flavors and fragrances are directly isolated from natural resources, such as plants or animals. Nature-identical flavors and fragrances have the same chemical composition as the natural counterpart but are synthetically produced via chemical or biotechnological methods. Artificial flavors and fragrances are synthetic compounds which do not exist in nature (Malik and Rawat, 2021). While the flavor and fragrance industry continues to develop novel aromas and tastes to meet consumer demand, there is an increasing concern about the potential adverse health and environmental effects of some chemically synthesized compounds. Many synthetic flavor and fragrances have unknown toxicological properties and may persist and accumulate in the environment (K R et al., 2022). This has driven a shift in the market toward safer production methods that can emulate the cost efficiency and production volumes of chemical synthesis while reducing risks (Paulino et al., 2021).

Arising from natural evolution, enzymes accelerate essential chemical transformations in life processes (Heckmann and Paradisi, 2020, Ali et al., 2020). They have also traditionally been used in the food industry to help unlock appealing flavors and tastes. With the development of modern biotechnology, enzymes are becoming indispensable catalysts for (bio)synthetic chemists due to their superior properties, including chemoselectivity, regioselectivity, stereoselectivity, mild reaction conditions, and reduced waste generation (Wu et al., 2021). Although native enzymes perform well under conditions relevant to the original hosts’ physiological conditions, they are limited in substrate scope, reaction rate, and stability in industrial applications. To overcome these issues, researchers have turned to protein engineering to generate enzymes with tailored substrate specificity, improved catalytic activity, as well as enhanced stability in organic solvents, raised temperature, and extended reaction time. (Fig. 1B) (Ali et al., 2020, Wu et al., 2021, Arnold, 2018, Hilvert, 2013, Reetz, 2022). In recent years, engineered enzymes have expedited the growth of the food industry. Several well-studied examples include lipases, proteases, alcohol dehydrogenases, and hydrolases (Paulino et al., 2021, Wu et al., 2021, SÁ et al., 2017, Sharma et al., 2021). This review summarizes progress in harnessing enzymes for flavor and fragrance synthesis, with a focus on two enzymes, i.e., carboxylic acid reductase (CAR) and unspecific peroxygenase (UPO). We start with a brief review of the current status of flavor and fragrance production, the background knowledge of the two enzymes’ structure, function, and applications, followed by an extensive discussion on recent engineering efforts to improve their industrial performance. We conclude the review with a summary and future perspectives on protein engineering and enzymatic for flavor and fragrance production applications.