With the rapid development of synthetic biology, genetic engineering, and molecular manipulation methods in recent years, microalgae, as representatives of microbial cell factories, have been widely used as hosts in the production of high-value bioproducts, such as oils, pigments, proteins, and biofuels, demonstrating promising prospects of application in biochemical energy, food and drugs, and environmental protection. Despite these advancements, the low production efficiency of microalgae limits their industrial application. In addition to strain improvement and culture condition optimization, the regulation by exogenous chemical additives serves as a promising optimization strategy. This method relies on straightforward phenotypic screening and circumvents the necessity for intricate understanding of molecular targets in the metabolic and catabolic pathways involved in the synthesis of bioproducts. It enables rapid yield increasing of high-value bioproducts from microalgae and obtaining the required phenotypes. Although studies have reported the use of alternatives means such as exogenous additives to improve the growth of microalgae and the yield of high-value bioproducts, the classification and summarization of the types, applications, targeted strains, and molecular mechanisms of these additives are not comprehensive. Here, we review the studies using chemical inducers or enhancers to improve cell growth and high-value bioproduct accumulation in microalgae in recent years. This paper focuses on the types of exogenous additives, the effects of exogenous additives and their combinations on microalgae growth and high-value bioproduct accumulation, and the molecular mechanisms of related effects. We aim to provide information for researchers to use methods of synthetic biology to develop suitable cell chassis and harness microalgae for industrial production.
Microalgae/drug effects* ; Biofuels

A system coupling ethanol fermentation with microalgae culture was developed, in which CO2 produced during ethanol fermentation was used as carbon source for the growth of Tetraselmis subcordiformis, a microalgae accumulating starch intracellularly. The biomass concentration about 2.0 g DCW/L was achieved within the photobioreactor for the batch culture of 7 days, and intracellular starch accumulation was about 45%. Furthermore, ultrasonic pretreatment and enzymatic hydrolysis were applied to the microalgae biomass, and 71.1% of the intracellular starch was converted into glucose that was fermented sequentially to ethanol by Saccharomyces cerevisiae with an ethanol yield of 87.6% of the theoretical value, indicating that the microalgae biomass could be an alternative feedstock for ethanol production to save grain consumption, and in the meantime mitigate the CO2 emission.
Batch Cell Culture Techniques ; Carbon Dioxide ; metabolism ; pharmacology ; Cells, Cultured ; Ethanol ; metabolism ; Fermentation ; Microalgae ; drug effects ; growth & development ; metabolism ; Photobioreactors ; Saccharomyces cerevisiae ; metabolism ; Starch ; metabolism