气候变化领域集成服务门户(CCPortal): The number of catalytic cycles in an enzyme’s lifetime and why it matters to metabolic engineering

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DOI	10.1073/pnas.2023348118
	The number of catalytic cycles in an enzyme’s lifetime and why it matters to metabolic engineering
	Hanson A.D.; McCarty D.R.; Henry C.S.; Xian X.; Joshi J.; Patterson J.A.; García-García J.D.; Fleischmann S.D.; Tivendale N.D.; Harvey Millar A.
发表日期	2021
ISSN	00278424
卷号	118 期号:13
英文摘要	Metabolic engineering uses enzymes as parts to build biosystems for specified tasks. Although a part’s working life and failure modes are key engineering performance indicators, this is not yet so in metabolic engineering because it is not known how long enzymes remain functional in vivo or whether cumulative deterioration (wear-out), sudden random failure, or other causes drive replacement. Consequently, enzymes cannot be engineered to extend life and cut the high energy costs of replacement. Guided by catalyst engineering, we adopted catalytic cycles until replacement (CCR) as a metric for enzyme functional life span in vivo. CCR is the number of catalytic cycles that an enzyme mediates in vivo before failure or replacement, i.e., metabolic flux rate/protein turnover rate. We used estimated fluxes and measured protein turnover rates to calculate CCRs for ∼100–200 enzymes each from Lactococcus lactis, yeast, and Arabidopsis. CCRs in these organisms had similar ranges (<103 to >107) but different median values (3–4 × 104 in L. lactis and yeast versus 4 × 105 in Arabidopsis). In all organisms, enzymes whose substrates, products, or mechanisms can attack reactive amino acid residues had significantly lower median CCR values than other enzymes. Taken with literature on mechanism-based inactivation, the latter finding supports the proposal that 1) random active-site damage by reaction chemistry is an important cause of enzyme failure, and 2) reactive noncatalytic residues in the active-site region are likely contributors to damage susceptibility. Enzyme engineering to raise CCRs and lower replacement costs may thus be both beneficial and feasible. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Catalytic cycles; Energetic costs; Enzyme longevity; Protein turnover; Synthetic biology
语种	英语
scopus关键词	Arabidopsis; article; catalyst; enzyme activity; enzyme engineering; in vivo study; Lactococcus lactis; lifespan; longevity; metabolic engineering; nonhuman; protein metabolism; synthetic biology; yeast
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180090
作者单位	Horticultural Sciences Department, University of Florida, Gainesville, FL 32611, United States; Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, IL 60439, United States; Computation Institute, The University of Chicago, Chicago, IL 60637, United States; Industrial and Systems Engineering Department, University of FloridaFL 32611, United States; Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, University of Western Australia, Crawley, WA 6009, Australia
推荐引用方式 GB/T 7714	Hanson A.D.,McCarty D.R.,Henry C.S.,等. The number of catalytic cycles in an enzyme’s lifetime and why it matters to metabolic engineering[J],2021,118(13).
APA	Hanson A.D..,McCarty D.R..,Henry C.S..,Xian X..,Joshi J..,...&Harvey Millar A..(2021).The number of catalytic cycles in an enzyme’s lifetime and why it matters to metabolic engineering.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA	Hanson A.D.,et al."The number of catalytic cycles in an enzyme’s lifetime and why it matters to metabolic engineering".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).