Harnessing synthetic biology for tetraterpenoid astaxanthin production: Recent advances and challenges

Astaxanthin, a potent lipid-soluble ketocarotenoid, exists in various stereoisomeric, geometric isomeric, and esterified forms. Its unique molecular configuration and biological activity confer significant advantages for pharmaceutical applications and nutraceutical supplementation. While widely distributed in natural environments, particularly abundant in marine ecosystems, astaxanthin production via conventional methods fails to meet escalating market demands and consumer preference for natural products. Recent synthetic biology advances enable engineered microbial cell factories for astaxanthin production. Through precise genome editing and metabolic reprogramming, these systems offer a sustainable, efficient alternative to traditional synthesis of this high-value antioxidant. In this review, we highlight the latest advancements in constructing artificial cell factories for the production of astaxanthin. Specially, we systematically examine current breakthroughs in synthetic biology-enabled astaxanthin manufacturing, with emphasis on three dimensions: "point" (regulation of key enzymatic activity and expression levels), "line" (pathway-level spatial coordination to balance intermediate flux), and "plane" (system-level metabolic harmonization to address product toxicity and pathway-host metabolic incompatibility). We further discuss critical gaps requiring interdisciplinary innovation to realize the full potential of microbial cell factories in sustainable astaxanthin manufacturing production.