Abstract
Plant natural products have been used for centuries to treat human illnesses, as recreational substances, and as flavoring and coloring agents in our food. Nowadays, commercial-scale manufacturing of plant natural products using extraction from natural resources or chemical synthesis poses challenges for environmental sustainability, such as species overexploitation. Bio-based synthesis of plant natural products in microbial cell factories can offer an attractive alternative as these processes reduce the use of natural plant resources and instead rely on renewable feedstocks as raw materials. Here, we review the most recent developments on the sustainable supply of plant natural products by the bio-based synthesis in yeast, with a special focus on newly discovered and implemented plant natural product biosynthetic pathways, approaches for chemical diversification of natural products, and optimization of platform yeast cell factories. From this, we discuss environmental considerations and the main challenges toward sustainable and robust microbial production of plant natural products based on fermentation.
Highlights
Natural Products (NPs) of plants encompass a diverse set of secondary metabolites, including polyketides, alkaloids, terpenes, and aromatic compounds [1]
We focus on recent advances in NP pathway discovery and engineering of microbial cell factories for NP biosynthesis
We focus on the budding yeast, Saccharomyces cerevisiae, a preferred host for the chemical biosynthesis of plant NPs
Summary
Natural Products (NPs) of plants encompass a diverse set of secondary metabolites, including polyketides, alkaloids, terpenes, and aromatic compounds [1]. Some NPs are produced at an industrial scale and are widely used Examples of this include (1) 22.7% of drugs approved by the US Food and Drug Administration in the last 40 years are NP or derivatives of them [2], and the annual production of 20,000 metric tons of synthetic vanillin [3], perhaps the most used natural flavor ingredient in use. We focus on recent advances in NP pathway discovery and engineering of microbial cell factories for NP biosynthesis For the latter point, we focus on the budding yeast, Saccharomyces cerevisiae, a preferred host for the chemical biosynthesis of plant NPs. We highlight some of the most prominent technical and environment-related challenges within the development of commercial-scale NP microbial cell factories and directions for mitigations
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