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Systems Analysis of Microbial Adaptations to Simultaneous Stresses

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Reprogramming Microbial Metabolic Pathways

Part of the book series: Subcellular Biochemistry ((SCBI,volume 64))

Abstract

Microbes live in multi-factorial environments and have evolved under a variety of concurrent stresses including resource scarcity. Their metabolic organization is a reflection of their evolutionary histories and, in spite of decades of research, there is still a need for improved theoretical tools to explain fundamental aspects of microbial physiology. Using ecological and economic concepts, this chapter explores a resource-ratio based theory to elucidate microbial strategies for extracting and channeling mass and energy. The theory assumes cellular fitness is maximized by allocating scarce resources in appropriate proportions to multiple stress responses. Presented case studies deconstruct metabolic networks into a complete set of minimal biochemical pathways known as elementary flux modes. An economic analysis of the elementary flux modes tabulates enzyme atomic synthesis requirements from amino acid sequences and pathway operating costs from catabolic efficiencies, permitting characterization of inherent tradeoffs between resource investment and phenotype. A set of elementary flux modes with competitive tradeoffs properties can be mathe­matically projected onto experimental fluxomics datasets to decompose measured phenotypes into metabolic adaptations, interpreted as cellular responses proportional to the experienced culturing stresses. The resource-ratio based method describes the experimental phenotypes with greater accuracy than other contemporary approaches and further analysis suggests the results are both statistically and biologically significant. The insight into metabolic network design principles including tradeoffs associated with concurrent stress adaptation provides a foundation for interpreting physiology as well as for rational control and engineering of medically, environmentally, and industrially relevant microbes.

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Abbreviations

13C:

carbon 13

Cfumarate :

concentration of fumarate

Cinv :

carbon investment

Cmole:

carbon mole

Cmol glc:

Cmol glc, carbon moles of glucose

Cmol X:

Cmol X, carbon moles of biomass

Cop,X :

carbon operating cost for growth

M :

micromoles of carbon per liter of cytosol

E :

matrix containing ecologically important elementary modes

[E]:

enzyme concentration

EFM:

elementary flux mode

EFMA:

elementary flux mode analysis

FBA:

flux balance analysis

kcat :

catalytic turnover number

Km :

half-saturation constant

MFA:

metabolic flux analysis

Ninv :

nitrogen investment

Ninv,X,1:1 :

nitrogen investment for growth, minimalist flux-to-enzyme approach

O2,op,X :

oxygen operating cost for growth

ν :

vector containing fluxes

vmax :

maximum enzyme-catalyzed reaction rate

w :

vector containing weighting factors

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Carlson, R.P., Oshota, O.J., Taffs, R.L. (2012). Systems Analysis of Microbial Adaptations to Simultaneous Stresses. In: Wang, X., Chen, J., Quinn, P. (eds) Reprogramming Microbial Metabolic Pathways. Subcellular Biochemistry, vol 64. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5055-5_7

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