中科院天工所戴住波、张学礼：维生素A（视黄酸）高效酵母细胞工厂

Core Viewpoint - All-trans retinoic acid (ATRA) is a key active derivative of vitamin A with extensive clinical application value, but mainstream manufacturers like BASF and DSM still rely on traditional chemical synthesis methods, which pose environmental challenges and do not meet green chemistry requirements [1][3]. Group 1: Research Breakthroughs - The team from the Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, achieved a breakthrough by engineering Saccharomyces cerevisiae to produce ATRA at a fermentation yield of 1.84 g/L, providing a green solution for constructing a self-controlled vitamin industry chain [3][8]. - The research utilized a multi-faceted metabolic engineering strategy, optimizing chassis construction, module selection, cellular factory upgrades, and fermentation processes to achieve this yield [8]. Group 2: Metabolic Engineering Strategy - The initial focus was on creating a high-yield chassis for β-carotene, the precursor for ATRA, by screening genes from Xanthophyllomyces dendrorhous, leading to the construction of the Car09 strain with a β-carotene yield of 129.4 mg/L [5][6]. - The best combination for ATRA synthesis was identified as a β-carotene dioxygenase from marine bacteria and mouse retinaldehyde dehydrogenase, achieving 98.1 mg/L ATRA, although significant residual β-carotene indicated limitations in synthesis [6][7]. Group 3: Industrial Adaptation and Optimization - Four-dimensional collaborative modifications were implemented to address efficiency bottlenecks, including overexpressing transcription factors to enhance endoplasmic reticulum activity, balancing NADPH/NAD⁺ levels, and improving substrate supply, resulting in a 49.2% increase in ATRA yield [7][8]. - The development of a two-phase extraction fermentation process, combining glucose growth with ethanol and galactose induction, led to the successful production of ATRA at 1.84 g/L in a 5L fermenter [8]. Group 4: Industry Conference - The SynBioCon 2025 conference, scheduled for August 20-22 in Ningbo, will focus on the intersection of AI and biological manufacturing, exploring trends in green chemistry, new materials, future food, agriculture, and cosmetic ingredients [10][12].