caa a22 4500 605499551 CHVBK 20210128100551.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00253-015-6791-y doi (NATIONALLICENCE)springer-10.1007/s00253-015-6791-y Highly efficient biosynthesis of astaxanthin in Saccharomyces cerevisiae by integration and tuning of algal crtZ and bkt [Elektronische Daten] [Pingping Zhou, Lidan Ye, Wenping Xie, Xiaomei Lv, Hongwei Yu] Astaxanthin is a highly valued carotenoid with strong antioxidant activity and has wide applications in aquaculture, food, cosmetic, and pharmaceutical industries. The market demand for natural astaxanthin promotes research in metabolic engineering of heterologous hosts for astaxanthin production. In this study, an astaxanthin-producing Saccharomyces cerevisiae strain was created by successively introducing the Haematococcus pluvialis β-carotenoid hydroxylase (crtZ) and ketolase (bkt) genes into a previously constructed β-carotene hyperproducer. Further integration of strategies including codon optimization, gene copy number adjustment, and iron cofactor supplementation led to significant increase in the astaxanthin production, reaching up to 4.7mg/g DCW in the shake-flask cultures which is the highest astaxanthin content in S. cerevisiae reported to date. Besides, the substrate specificity of H. pluvialis CrtZ and BKT and the probable formation route of astaxanthin from β-carotene in S. cerevisiae were figured out by expressing the genes separately and in combination. The yeast strains engineered in this work provide a basis for further improving biotechnological production of astaxanthin and might offer a useful general approach to the construction of heterologous biosynthetic pathways for other natural products. Springer-Verlag Berlin Heidelberg, 2015 Astaxanthin nationallicence Metabolic engineering nationallicence β-Carotenoid hydroxylase nationallicence β-Carotenoid ketolase nationallicence Saccharomyces cerevisiae nationallicence Haematococcus pluvialis nationallicence Zhou Pingping Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, 310027, Hangzhou, People's Republic of China aut Ye Lidan Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, 310027, Hangzhou, People's Republic of China aut Xie Wenping Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, 310027, Hangzhou, People's Republic of China aut Lv Xiaomei Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, 310027, Hangzhou, People's Republic of China aut Yu Hongwei Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, 310027, Hangzhou, People's Republic of China aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/20(2015-10-01), 8419-8428 0175-7598 99:20<8419 2015 99 253 https://doi.org/10.1007/s00253-015-6791-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-015-6791-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhou Pingping Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, 310027, Hangzhou, People's Republic of China aut NATIONALLICENCE 700 1- Ye Lidan Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, 310027, Hangzhou, People's Republic of China aut NATIONALLICENCE 700 1- Xie Wenping Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, 310027, Hangzhou, People's Republic of China aut NATIONALLICENCE 700 1- Lv Xiaomei Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, 310027, Hangzhou, People's Republic of China aut NATIONALLICENCE 700 1- Yu Hongwei Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, 310027, Hangzhou, People's Republic of China aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/20(2015-10-01), 8419-8428 0175-7598 99:20<8419 2015 99 253