SCyCode - Unraveling the cyanobacterial carbon switch and its regulation using enzyme kinetic analyses and mathematical modeling

SCyCode - 使用酶动力学分析和数学模型揭示蓝藻碳开关及其调节

基本信息

项目摘要

Synechocystis sp. PCC 6803 (hereafter named Synechocystis) possesses a broad metabolic versatility and is able to grow photoautrotrophic, heterotrophic as well as photomixotrophic. In addition to the auto- and heterotrophic diurnal rhythm, transitions from a photoautotrophic to a heterotrophic life style “autotrophy-heterotrophy switch” are also induced in response to inorganic carbon and nitrogen fluctuations.Notably, the Synechocystis primary metabolism is characterized by parallel pathways with partly shared enzyme reactions and multiple isoenzymes. Among the different pathways the Embden-Meyerhof-Parnas (EMP) pathway is the only reversible pathway with function in gluconeogenesis and glycolysis. In previous studies it was demonstrated that in Synechocystis the biochemical control likely dominates over the transcriptional control in order to adjust the central carbon metabolism to response to changed carbon availability. Hence, we hypothesized that these isoenzymes might possess different kinetic and regulatory properties to perform the autotrophy-heterotrophy switch. In the first funding period, we identified the two phosphofructokinase (PFK) and pyruvate kinase (PK) isoenzymes as well as phosphoglycerate kinase (PGK) as novel control points of the cyanobacterial EMP pathway. These studies were performed in close collaboration with Jacky Snoep (Co-PI) and the groups of Martin Hagemann and Kirstin Gutekunst. Our results hint at a complex regulation, which takes place and is governed by the energy charge of the cell, the availability of reduced/oxidized electron carrier (i.e. NAD(P)+ or NAD(P)H + H+) and the redox state of the cell (i.e. thioredoxin/ferredoxin). In addition, the cellular concentrations of key intermediates such as glucose 6-phosphate or 3-phosphoglycerate seems to play a significant role. The aim of this subproject in the second funding period is to provide additional detailed enzyme characterizations combined with detailed reaction kinetic mathematical models (Co-PI Jacky Snoep) in order to characterize these important control points that regulate the carbon flux in response to growth conditions, i.e. the autotrophy-heterotrophy switch. Therefore, we will focus on the antagonistic enzyme couples, and the triosephosphate hub as control points of the EMP pathway. In addition, the flux of glucose 6-phophate from glycogen or glucose into the EMP or alternative catabolic pathways as well as the regulation of the lower EMP shunt will be addressed. These studies will be performed in close collaboration with our SCyCode partners Karl Forchhammer, Sofia Doello, Martin Hagemann and Kirstin Gutekunst.
集胞藻属PCC 6803(以下简称集胞藻)具有广泛的代谢多样性,能够光合自养、异养和光合混合营养生长。除了自养和异养的昼夜节律外,从光合自养到异养的生活方式的“自养-异养开关”也被诱导以响应无机碳和氮的波动。值得注意的是,集胞藻的初级代谢具有部分共享的酶反应和多种同工酶的平行途径。在这些不同的途径中,Embden-Meyerhof-Parnas(EMP)途径是唯一一条在糖酵解和异生中起作用的可逆途径。在以前的研究中,它被证明,在集胞藻的生化控制可能占主导地位的转录控制,以调整中央碳代谢,以响应改变碳的可用性。因此,我们推测这些同工酶可能具有不同的动力学和调节特性,以执行自养-异养转换。在第一个资助期内,我们确定了两个磷酸果糖激酶(PFK)和丙酮酸激酶(PK)同工酶以及磷酸甘油酸激酶(PGK)作为蓝藻EMP途径的新控制点。这些研究是与Jacky Snoep(Co-PI)以及Martin Hagemann和Kirstin Gutekunst小组密切合作进行的。我们的研究结果暗示了一种复杂的调节,它发生并受细胞的能量电荷、还原/氧化电子载体(即NAD(P)+或NAD(P)H + H+)的可用性和细胞的氧化还原状态(即硫氧还蛋白/铁氧还蛋白)的控制。此外,关键中间体如葡萄糖6-磷酸或3-磷酸甘油酸的细胞浓度似乎起着重要作用。该子项目在第二个资助期内的目的是提供额外的详细酶表征,结合详细的反应动力学数学模型(Co-PI Jacky Snoep),以表征这些重要的控制点,这些控制点调节碳通量以响应生长条件,即自养-异养开关。因此,我们将重点放在拮抗酶对,和磷酸丙糖枢纽作为EMP途径的控制点。此外,葡萄糖6-磷酸从糖原或葡萄糖进入EMP或替代分解代谢途径的流量,以及较低的EMP分流的调节将得到解决。这些研究将与我们的SCyCode合作伙伴Karl Forchhammer、索菲亚Doello、Martin Hagemann和Kirstin Gutekunst密切合作进行。

项目成果

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Professorin Dr. Bettina Siebers其他文献

Professorin Dr. Bettina Siebers的其他文献

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{{ truncateString('Professorin Dr. Bettina Siebers', 18)}}的其他基金

The branched Entner-Doudoroff pathway in Thermoproteus tenax: Enzymes, regulation and physiological function
Thermoproteus tenax 中的分支 Entner-Doudoroff 途径:酶、调节和生理功能
  • 批准号:
    35244511
  • 财政年份:
    2007
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Functional and comparative genomics for the central carbohydrate metabolism of hyperthermophilic Archaea, presented in a new database
新数据库中提出了超嗜热古菌中央碳水化合物代谢的功能和比较基因组学
  • 批准号:
    5447818
  • 财政年份:
    2005
  • 资助金额:
    --
  • 项目类别:
    Priority Programmes

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    24K17065
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    2024
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CAREER: Unraveling the evolutionary history of toothed whale acoustic communication
职业:揭开齿鲸声音通讯的进化史
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