Microbial production of C₇-C₉ aromatic building blocks for the production of natural products

Covering: up to 2025Aromatic compounds have been widely applied in the production of plastics, pharmaceuticals, dyes, fragrances and cosmetics. Since conventional chemical synthesis of aromatic compounds relies on non-renewable fossil-based feedstocks and involves complex processes, microbial biosynthesis has emerged as a sustainable and efficient alternative. However, the complexity of the metabolic pathways of aromatic compounds, limited precursor supply, and the cytotoxicity of certain products severely constrain the efficient production of target compounds. To address these bottlenecks, various metabolic engineering strategies have been developed, which include modular pathway design to enhance metabolic flux coordination and flexibility, the introduction of novel biosynthetic pathways to expand the substrate spectrum, and evolutionary engineering approaches to improve host strain tolerance to product-induced toxicity. In this review, we systematically introduce the application potential of representative C₇-C₉ aromatic compounds, elucidate their biosynthetic pathways, analyze the specific challenges inherent to each compound, and summarize the recent progress in metabolic engineering strategies. We further discuss emerging strategies in light of the current state-of-the-art developments in microbial aromatic biosynthesis, incorporating comparisons between microbial and petrochemical production in industrial applications to outline future directions for aromatic compound biosynthesis.