title: Sequential control of biosynthetic pathways for balanced utilization of metabolic intermediates in Saccharomyces cerevisiae.
abstract: Balanced utilization of metabolic intermediates and controllable expression of genes in biosynthetic pathways are key issues for the effective production of value-added chemicals in microbes. An inducer/repressor-free sequential control strategy regulated by glucose concentration in the growth environment was proposed to address these issues, and its efficiency was validated using heterologous beta-carotenoid biosynthesis in Saccharomyces cerevisiae as an example. Through sequential control of the downstream, upstream, and competitive pathways of farnesyl diphosphate (FPP), the crucial metabolic node in the biosynthesis of terpenoids, in a predetermined order, a carotenoid production of 1156 mg/L (20.79 mg/g DCW) was achieved by high-cell density fermentation. Quantitative PCR analysis of the regulated genes demonstrated that the transcription patterns were controlled in a sequential manner as expected. The inducer/repressor-free nature of this strategy offers a both practical and economically efficient approach to improved biosynthetic production of value-added chemicals.
authors.affiliation: Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Xie
authors.affiliation: Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China; Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Lidan
authors.initials: L
authors.lastname: Ye
authors.affiliation: Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Lv
authors.affiliation: Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Haoming
authors.initials: H
authors.lastname: Xu
authors.affiliation: Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China. Electronic address: yuhongwei@zju.edu.cn.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yu
mesh_terms: D002338:Carotenoids / Q000096:biosynthesis / Q000235:genetics; D060847:Metabolic Engineering; D011106:Polyisoprenyl Phosphates / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D012717:Sesquiterpenes / Q000378:metabolism*
chemical_list: D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; D002338:Carotenoids; C004808:farnesyl pyrophosphate
keywords: Biosynthetic pathway; Carotenoids; Metabolic engineering; Sequential control