# Biosynthesis of Edible Terpenoids: Hosts and Applications
## 4 Conclusions and Perspectives  
Microbial cell factories have the capability to utilize cost-effective raw materials, even one-carbon materials, for the production of fine chemicals. This offers a green and sustainable platform for terpenoid production. It is essential to study natural biosynthetic pathways, analyze key enzymes and regulatory mechanisms in these pathways, and heterologously integrate them into microbial chassis cells to construct cell factories. Large-scale production via fermentation is an important strategy to meet the market demand for edible terpenoids. In recent years, scientists have been dedicated to engineering typical or non-typical microbial hosts to produce various types of terpenoids and their derivatives [10; 134; 135; 10]. To further exploit the potential of microbial cells in edible terpenoid production, the following aspects should be taken into consideration. First and foremost, the selection of the host is paramount. An excellent chassis can potentially double outcomes with half exertion. Selecting strains that are GRAS can, to a certain extent, avoid evaluations on food safety. For instance, _Lactococcus lactis_, a common probiotic found in fermented food, can serve as a food supplement to directly deliver active molecules to the intestine. Researchers have already constructed a pathway for lycopene production in _L. lactis_ and preliminarily verified its potential in treating intestinal oxidative damage [136]. On the other hand, the selection of a precursor-rich chassis host can significantly reduce trial and error costs. Strains with abundant acetyl-CoA derivatives not only supply sufficient precursors for the terpenoid pathway but also, the metabolites derived from acyl-CoA derivatives, such as lipids, provide a hydrophobic environment for the cells conducive to the accumulation of terpenoids. Terpenoids such as monoterenes, sesquiterpenes, and diterpenes have their respective common important intermediates in the synthetic pathway. Direct metabolic switching in existing cell factories can accelerate the strain construction process. Secondly, reprogramming the biosynthetic pathway of terpenoids is essential. Terpenoids have diverse and complex structures. During evolution, in order to optimize the metabolic efficiency of organisms and reduce the number of unnecessary enzymes, terpenoid synthases responsible for forming the terpenoid skeleton and downstream modification enzymes often exhibit promiscuity or are bifunctional enzymes. Hence, even when a terpenoid synthesis pathway is heterologously introduced into a microbial host, there remains a potential for unexpected components. Mining enzymes with more specific functions can enhance the yield of target products and facilitate subsequent separation and purification. Nowadays, numerous strategies have been developed for mining the biosynthetic gene clusters from natural products [137]. On the other hand, to establish novel terpenoid synthesis pathways, it is crucial to identify enzymes from various species or to develop multifunctional enzymes. The rise of artificial intelligence technology enables the customization of enzymes with specific catalytic functions [138]. Moreover, preliminary advancements have been achieved in discovering and reconstructing non-typical terpenoid compound biosynthetic pathways by deep learning [139; 140; 141]. Considering that the formation and modification of terpenoid skeletons require multi-enzyme cascade reactions, strategies such as compartmentalization, membrane-less organelles, and protein scaffolds can potentially elevate metabolic rates [142; 143]. In addition, high-throughput screening techniques offer rapid identification of strains with high-yield and high-titer. Distinct from traditional metabolite extraction followed by mass spectrometry detection, screening approaches based on biosensors [144] and growth-coupling [77] have significantly increased the screening throughput of microbial libraries.