Microbial Metabolism • Metabolism in Cellular Context • Types of Microbial Metabolism (Catabolism) • How Microbes use Energy • Link between Thermodynamics and Kinetics • Speciation of Metabolic pathways • Metabolism in Natural Selection and Isolation of Microbes What constrains microbial metabolism? Today Next Thursday • Principles of Metabolic Transformations • Patterns of Metabolism Chemical constraints microbial metabolism KITP Forum Microbial Metabolism 2021
46
Embed
KITP Forum Microbial Metabolism 2021 Microbial Metabolism
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Microbial Metabolism
• Metabolism in Cellular Context
• Types of Microbial Metabolism (Catabolism)
• How Microbes use Energy
• Link between Thermodynamics and Kinetics
• Speciation of Metabolic pathways
• Metabolism in Natural Selection and Isolation of Microbes
What constrains microbial metabolism?
Today
Next Thursday
• Principles of Metabolic Transformations
• Patterns of MetabolismChemical constraints microbial metabolism
KITP Forum Microbial Metabolism 2021
What of metabolism is it that we want to understand?
Metabolism
Physiology Ecology
KITP Forum Microbial Metabolism 2021
Nothing in biology makes sense except in light of evolution
Theodosius Dobzhansky, 1973
Life is nothing but an electron looking for a place to rest.
Albert Szent-Gyorgi
Selection is everywhereJohn Roth (paraphrased)
KITP Forum Microbial Metabolism 2021
It’s not!!!
Why is metabolism complicated?
We need some order!!
… but it looks complicated?
R2
R1 COH
H R2R1 CO
HCO
OCO
R2R1R1
C CO
CRH
H
H
HS-CoA C C
OCRH
HS-CoA
Alcohol oxidation
Aldehyde oxidation
Acyl-CoA oxidation
Oxygenation
CH
HR1 H + 2[H]
H
CO
HR1 H
O2
+ H2O
CCH
H
H
HCH
HR1 H CC
H
H HCH
R1 H
OH OHO2
Methyl-CoM reduction
CH3-S-CoM + H-S-CoB CoM-S-S-CoB + CH4
S-CoAOS-CoAOFd2 + Energy (ATP or via electron bifurcation)
Benzoyl-CoA reduction (dearomatizing)
Oxidations/reductions
+ H- + H+
+ H- + H+
R1R2 CO H
H
R1CO
Hemiacetal oxidation
+ H- + H+O R2 O
R CC
H O
H
H
H
HCO
CO
H
CH
HH+ HR
R CH
H
H
HC H+H
H
CH
CO
H O
CO
CO
H
R CO
Aldol cleavage
Ketol cleavage
Fumarate additionCOO-
-OOC CCH
H
R
CH
H
COO--OOC CCH
H
RC RH
H+ R
CO + HS-CoA + CH3 - H4F CH3CO-S-CoA + H4F
CO2 + Fd2- +2H+ Fd + H2O + CO
De/carbonylation
C-C cleavage/condensations
1
2
1
2
CR CCH
HR2
OCCR
H
H
H
NuNu-
CO
R2
CC
H
H H
R2R1
R3
CC
H
R2R1
R3
H H
Rearrangement
Nucleophilic addition/elimination
C COH
S-CoA
OH
CR
H
H
C CO
CH
HS-CoAR
H2O
a hydroxy elimination
Auxiliary reactions
Hydrogen oxidation
H2 2 e- + 2 H+
Com
plex
ity o
f org
anic
subs
trate
Module (more than one prototypic enzymatic reaction)
Single, less common enzymatic reaction
= Module
Pathway
A
B
Single prototypic enzymatic reaction
o Pathway node
o
o
o
oo Com
plex
ity o
f org
anic
subs
trate
Module (more than one prototypic enzymatic reaction)
Single, less common enzymatic reaction
= Module
Pathway
A
B
Single prototypic enzymatic reaction
o Pathway node
o
o
o
oo
Modularity of Catabolic PathwaysKITP Forum Microbial Metabolism 2021
S1
P2P1
n[H]
ATP
Anabolic Substrates(C, N, S..)S2
[H]
Inter-mediates
ATP
General
Catabolic and Anabolic PathwaysKITP Forum Microbial Metabolism 2021
S1
P2P1
n[H]
ATP
S2
[H]
Inter-mediates
ATP
Monomers(amino acids, nucleotides, long
chain fatty acids, carbohydrates,…)
Polymers(proteins, RNA, DNA,
lipids, peptidoglycan,…)
Anabolic Substrates(C, N, S..)
Transport, Adjusting oxidation state,Forming covalent C-C, C-N, etc. bonds
ATP-dependent polymerizations via H2O abstraction
Folding, transport/export
Catabolic and Anabolic PathwaysKITP Forum Microbial Metabolism 2021
Biosynthetic precursors of amino acids,nucleic acids, and cofactors
4 H2 + CO2 + nATP ADP + nATP Pi CH4 + nATP ATP + 3 H2ODG’nATP=0 - 131 kJ/mol
nATP = 0
nATP = 0.5
nATP = 1.0
DGS->P=nATPDGATP +DGheat
ATP ATP ATP
nATPS I1 I2 I3 I4 I5 PATP
KITP Forum Microbial Metabolism 2021
A link between thermodynamics (nATP) and kinetics (flux JS)
Ecological success and microbial growth- Relationship between growth, available energy, and growth rate -
In thermodynamic equilibrium, 0, and
Available energy:
S … PATP ATP ATP
1 2 nATP
Pfeiffer & Bonhoeffer 2002, Costa et al 2006
KITP Forum Microbial Metabolism 2021
Ecological success and microbial growth- Relationship between growth, available energy, and growth rate -
Fluxes (rates):
In thermodynamic equilibrium, JS and JATP = 0However at yields nATP lower than nmax, <0 and drives the reaction, and consequently, JS and JATP become positive.
In thermodynamic equilibrium, 0, and
Available energy:
S … PATP ATP ATP
1 2 nATP
Pfeiffer & Bonhoeffer 2002, Costa et al 2006
KITP Forum Microbial Metabolism 2021
Rate versus yield tradeoff- for fundamental thermodynamic reasons, irrespective of the pathway -
ATP yield
Rate
of s
ubst
rate
util
izatio
nAT
P pr
oduc
tion
Pfeiffer & Bonhoeffer 2002
KITP Forum Microbial Metabolism 2021
Competition favors rate over yield
P = pay-off, total amount of ATP produced from a given amount of resource S for a given strategy nATP
P under non-competitive conditions
Pay-off for a given strategy is determined only by its yield but not its rate of ATP production
P under competitive conditions
If JC is small, P is large if JS is small; i.e., if competition is small, a slow strategy for efficient ATP formation is advantageous.
If JC is large, a more efficient pathway (nATP) will not significantly reduce JS, and strategies with high rates but lower yields will result in higher pay-off.
Size of a population is determined by yield; outcome of competition is determined by rate of ATP production