title: A new paradigm for producing astaxanthin from the unicellular green alga Haematococcus pluvialis.
abstract: The unicellular green alga Haematococcus pluvialis has been exploited as a cell factory to produce the high-value antioxidant astaxanthin for over two decades, due to its superior ability to synthesize astaxanthin under adverse culture conditions. However, slow vegetative growth under favorable culture conditions and cell deterioration or death under stress conditions (e.g., high light, nitrogen starvation) has limited the astaxanthin production. In this study, a new paradigm that integrated heterotrophic cultivation, acclimation of heterotrophically grown cells to specific light/nutrient regimes, followed by induction of astaxanthin accumulation under photoautotrophic conditions was developed. First, the environmental conditions such as pH, carbon source, nitrogen regime, and light intensity, were optimized to induce astaxanthin accumulation in the dark-grown cells. Although moderate astaxanthin content (e.g., 1% of dry weight) and astaxanthin productivity (2.5 mg L(-1)  day(-1) ) were obtained under the optimized conditions, a considerable number of cells died off when subjected to stress for astaxanthin induction. To minimize the susceptibility of dark-grown cells to light stress, the algal cells were acclimated, prior to light induction of astaxanthin biosynthesis, under moderate illumination in the presence of nitrogen. Introduction of this strategy significantly reduced the cell mortality rate under high-light and resulted in increased cellular astaxanthin content and astaxanthin productivity. The productivity of astaxanthin was further improved to 10.5 mg L(-1)  day(-1) by implementation of such a strategy in a bubbling column photobioreactor. Biochemical and physiological analyses suggested that rebuilding of photosynthetic apparatus including D1 protein and PsbO, and recovery of PSII activities, are essential for acclimation of dark-grown cells under photo-induction conditions. Biotechnol. Bioeng. 2016;113: 2088-2099. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.
authors: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.|Department of Human System and Environment, Arizona State University, Mesa, Arizona.
authors: Zhen
authors: Z
authors: Zhang
authors: Department of Human System and Environment, Arizona State University, Mesa, Arizona.|Department of Chemical and Biochemical Engineering, Xiamen University, Xiamen, Fujian, China.
authors: Baobei
authors: B
authors: Wang
authors: Center for Microalgal Biotechnology and Biofuels, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei, China.
authors: Qiang
authors: Q
authors: Hu
authors: Department of Human System and Environment, Arizona State University, Mesa, Arizona.
authors: Milton
authors: M
authors: Sommerfeld
authors: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China. ygli@ecust.edu.cn.
authors: Yuanguang
authors: Y
authors: Li
authors: Center for Microalgal Biotechnology and Biofuels, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei, China. danxianghan@ihb.ac.cn.
authors: Danxiang
authors: D
authors: Han
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods; D000460:Chlorophyta / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D008027:Light; D009584:Nitrogen / Q000378:metabolism*; D010775:Photic Stimulation / Q000379:methods; D058433:Photobioreactors / Q000382:microbiology*; D010788:Photosynthesis / Q000502:physiology* / Q000528:radiation effects; D011829:Radiation Dosage; D024341:Xanthophylls / Q000096:biosynthesis / Q000302:isolation & purification / Q000528:radiation effects
chemical_list: D024341:Xanthophylls; C005948:astaxanthine; D009584:Nitrogen
keywords: Haematococcus pluvialis; acclimation; astaxanthin; heterotrophy