Terpenoids are a large class of plant-derived compounds, that constitute the main components of essential oils and are widely used as natural flavors and fragrances. The biosynthesis approach presents a promising alternative route in terpenoid production compared to plant extraction or chemical synthesis. In the past decade, the production of terpenoids using biotechnology has attracted broad attention from both academia and the industry. With the growing market of flavor and fragrance, the production of terpenoids directed by synthetic biology shows great potential in promoting future market prospects. Here, we reviewed the latest advances in terpenoid biosynthesis. The engineering strategies for biosynthetic terpenoids were systematically summarized from the enzyme, metabolic, and cellular dimensions. Additionally, we analyzed the key challenges from laboratory production to scalable production, such as key enzyme improvement, terpenoid toxicity, and volatility loss. To provide comprehensive technical guidance, we collected milestone examples of biosynthetic mono- and sesquiterpenoids, compared the current application status of chemical synthesis and biosynthesis in terpenoid production, and discussed the cost drivers based on the data of techno-economic assessment. It is expected to provide critical insights into developing translational research of terpenoid biomanufacturing.
