Engineered microbial production of carotenoids and their cleavage products: Recent advances and prospects

Carotenoids are a diverse group of tetraterpenoid compounds containing 40 carbon atoms commonly found in plants, fungi, bacteria, and algae (Mussagy et al., 2019). The Carotenoid Database (http://carotenoiddb.jp) currently lists information on 1204 natural carotenoids from 722 organisms. Most naturally occurring carotenoids are tetraterpenoids comprising eight isoprene units. Based on their chemical structure, carotenoids can be classified into oxygenated carotenoids (e.g., lutein and astaxanthin) and non‑oxygenated carotenoids (e.g., β-carotene and lycopene) (Jing et al., 2022; Mata-Gómez et al., 2014). Carotenoid cleavage products primarily include C30 β-apo-carotenal, C20 vitamin A, C8–C13 apocarotenoid volatiles and plant hormones such as strigolactones. Because of their distinctive fragrance, vibrant color, high nutritional value, and favorable physicochemical properties, carotenoids and apocarotenoids are widely used in various industrial products, including animal feeds, foods, pharmaceuticals, cosmetics, nutritional supplements, and biofuels (Cao et al., 2023; Cataldo et al., 2016; Debnath et al., 2024; Hong et al., 2015; Kapoor and Ramamoorthy, 2021).

The global annual revenue of the carotenoid market is projected to reach 200 million USD by 2026 (Zhang et al., 2023b). The demand for apocarotenoids, such as retinol and α/β-ionone, is also anticipated to grow rapidly (Qi et al., 2023). Although carotenoids and apocarotenoids are abundant in nature, their intracellular concentrations are very low. The main methods for producing these compounds are plant extraction, chemical synthesis, and microbial biosynthesis. Traditional extraction methods involve complex separation and purification processes, whereas chemical synthesis faces challenges such as high energy consumption, low efficiency, environmental impact, and the generation of toxic byproducts (Park et al., 2022a; Zhang et al., 2018a). Moreover, some synthetic carotenoids exhibit inferior structural stability and bioactivity compared to their natural counterparts (Zhang et al., 2018b). In contrast, microbial biosynthesis has emerged as a sustainable and efficient alternative with great potential (Jiang and Wang, 2023; Zhou et al., 2025), which can be achieved using naturally carotenoid-producing microorganisms or metabolically engineered host strains (Zhou et al., 2025). Microorganisms capable of naturally accumulating carotenoids include microalgae (e.g., Dunaliella salina, Haematococcus pluvialis, and Chlamydomonas reinhardtii), bacteria (e.g., Erwinia uredovora, Rhodobacter sphaeroides, and Paracoccus carotinifaciens), and fungi (e.g., Xanthophyllomyces dendrorhous and Blakeslea trispora) (Xu et al., 2018; Zhao et al., 2019). Commercialized carotenoid products derived from natural carotenoid-producing microorganisms include astaxanthin from H. pluvialis, X. dendrorhous and P. carotinifaciens, β-carotene from D. salina and B. trispora, and lycopene from B. trispora (Gong and Bassi, 2016; Wang et al., 2024a). These natural producers possess inherent advantages such as high accumulation capacity, complete metabolic pathways, and strong environmental adaptability, and are supported by relatively mature fermentation processes. However, issues such as limited product diversity, high production costs, and low genetic tractability hinder their broader application in producing high-value carotenoids and apocarotenoids (Eun et al., 2025; Zhou et al., 2025). With the advancement of metabolic engineering and synthetic biology, researchers have successfully reconstructed heterologous carotenoid and apocarotenoids biosynthetic pathways in various microbial hosts (Bu et al., 2020; Chen et al., 2025; Huang et al., 2022; Ma et al., 2022a). Since the first report of heterologous β-carotene production in Escherichia coli in the 1990s (Misawa et al., 1990), strategies such as key enzyme expression optimization, modular pathway design, enhanced precursor supply, and fermentation process optimization have enabled significant improvements in carotenoid yields, increasing from milligram to gram scale for β-carotene, lycopene, lutein, and other carotenoids (Eun et al., 2025; Ma et al., 2022b; Zhu et al., 2022) (Table 1).

In summary, heterologous microbial biosynthesis has emerged as one of the most promising strategies for the production of carotenoids and apocarotenoids. The aim of this review is to systematically consolidate the dispersed research on the heterologous biosynthesis of carotenoids and apocarotenoids, providing a comprehensive and structured perspective for the development of efficient biosynthetic systems for these compounds. It presents an overview of the biosynthetic pathways of carotenoids and apocarotenoids, starting with the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways, emphasizing the key enzymes involved in carotenoid cleavage. It also highlights effective methods and strategies to enhance carotenoid and apocarotenoid production, along with examples of microbial synthesis. Finally, we discuss future directions for the development of engineered microorganisms for carotenoid and apocarotenoid biosynthesis, offering valuable insights for future research in this field.

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