Advances and challenges in building microbial cell factories for phytohormone biomanufacturing toward sustainable...

The long-term and extensive use of conventional chemical pesticides has led to a series of problems, including pesticide resistance in plant pathogens and insect pests, environmental pollution, and risks to the safety of agricultural products. These challenges have created an urgent need for green, efficient, and sustainable alternative pest management strategies. As endogenous signaling molecules, phytohormones play crucial roles in regulating plant growth and development, enhancing stress tolerance, and inducing disease resistance. Owing to their environmental compatibility, target specificity, and biodegradability, phytohormones have emerged as promising candidates for the development of green agrochemicals. This review systematically summarizes the classification, biological functions, and biosynthetic pathways of the major phytohormones, including abscisic acid, gibberellins, jasmonic acid, salicylic acid, auxins, and others. Particular emphasis is placed on synthetic biology strategies for producing phytohormones using microbial cell factories, including promoter engineering, cofactor engineering, transporter engineering, dynamic regulation, cytochrome P450 engineering, subcellular compartmentalization, protein engineering and automation and artificial intelligence engineering. In addition, the major challenges associated with microbial production of phytohormones are discussed, such as the low activity of heterologously expressed cytochrome P450 and the complexity of subcellular compartmentalization. The review further highlights the potential applications of automation, machine learning, and artificial intelligence in accelerating the development of microbial cell factories and optimizing metabolic networks and fermentation processes. Finally, future directions for the industrial-scale production of phytohormones are proposed from three perspectives: efficient product recovery, the development of advanced synthetic biology tools, and AI-enabled biomanufacturing technologies.