origins and evolution of bioactive molecules chemical signalling n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Origins and Evolution of Bioactive Molecules (Chemical Signalling ) PowerPoint Presentation
Download Presentation
Origins and Evolution of Bioactive Molecules (Chemical Signalling )

Loading in 2 Seconds...

play fullscreen
1 / 24

Origins and Evolution of Bioactive Molecules (Chemical Signalling ) - PowerPoint PPT Presentation


  • 111 Views
  • Uploaded on

Origins and Evolution of Bioactive Molecules (Chemical Signalling ). Antibiotic resistance plasmids. Penicillinase discovery. ?. Increasing Antibiotic Resistance. 1940. 1950. 1960. 1970. 1980. 1990. 2000. Primordial. Golden. Biochemical. Target. Genomic HTS. Pharmacologic.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Origins and Evolution of Bioactive Molecules (Chemical Signalling )' - doria


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
a brief history of antibiotics co evolution of antibiotics and their resistance

Antibiotic resistance plasmids

Penicillinase

discovery

?

Increasing Antibiotic Resistance

1940

1950

1960

1970

1980

1990

2000

Primordial

Golden

Biochemical

Target

Genomic

HTS

Pharmacologic

Disenchantment

The Dark Ages

(Semmelweis)

(Semmelweis)

(again!)

FDA Office of

New Drugs

A brief history of antibiotics(co-evolution of antibiotics and their resistance)

Transmissible

fluoroquinolone

resistance

THE LEAN YEARS

*

**

MRSA: UK*, US**

Production: 50kg……………………………………………………………………………>106 tons

slide3

Side Effects of Streptomycin

Headache

Nausea

Hearing difficulties, deafness

Ringing sensation in the ears

Loss of balance

Fatigue

Difficulty in passing urine

Itchy rashes on the skin

but it cured TB!

Albert Schatz and Selman Waksman

Who deserved the Prize?

fifty years of industrial research on antibiotics
Fifty years of “Industrial Research” on Antibiotics

Environmental

Doubling time: months

Aeration: low

Nutrients: variable

Carbohydrate: limited

Water: variable

Temperature: 0-40

pH: 2-10

Yield: µgrams

Production

Doubling time: hours

Aeration: high

*Nutrients: high and constant

Carbohydrate: high

Water: unlimited

Temperature: 25-30

pH: 6-7

Yield: grams

*Typical substrates for fermentation

Molasses (blackstrap)

Fish Meal (herring, anchovy)

Citrus pulp

Asparagus juice

Cottonseed oil

Malt extract

Beef extract

Bovine blood

Pork liver

Distillers solubles

Hydrolysed rabbit fur

some numbers
SOME NUMBERS

(Revised from Kyrpides, 2009)

slide7

Inter-Kingdom Signalling

The Parvome

(Rumbaugh, 2007)

origins and evolution of bioactive small molecules
Origins and Evolution of Bioactive Small Molecules
  • Distribution: universal, ancient
  • Bioactivities: wide range, concentration-dependence
  • Receptors: mostly macromolecules (cross-species)
  • Structures: small number of major classes (with decoration)
  • Biosynthesis: frequently “assembly line”
  • Properties and applications: multitudinous
b io chemical evolution
(bio)Chemical Evolution

Hadean Period

Meteorites and

primordial

reactions

(RNA World)

Ribozymes

LUCA

(Last Universal Common Ancestor)

“Specialised” Microbial & Plant

Metabolism

Primary Secondary

(Modern) Tree of Life

the tree of life
The Tree of Life

Bacteria Eukaryotes Archaea

Mouse

Crenarchaeota

Amitochondriate

-0.1

Gram positives

Proteobacteria

Plants

Euryarchaeota

Cyanobacteria

Drosophila

0.1

Age of Dinosaurs

Cambrian

Precambrian

1.0

Origin of Metazoans

-1.0

20% [O2]

Origin of Eukaryotes

1.5

Increasing

[O2]

in atmosphere

2.1

-2.0

2.3

?

Origin of oxygenic

photosynthesis

-3.0

Anoxic

(H2, NH3, CO2,)

3.8

Last common ancestor

-4.0

Origin of Prokaryotes

Chemical evolution/

Prebiotic synthesis of biomolecules

Origin of Earth (4.5 Billion years)

slide13

MODULAR ASSEMBLY LINES

FOR BIOACTIVE COMPOUNDS

Polyketide synthase

Tetracycline, rapamycin, erythromycin

Nonribosomal peptide synthase

Daptomycin, polymixin, vancomycin

slide14

Carbonaceous meteorites

as sources of

chemical intermediates

Pizzarello & Shock (2010)

primordial amino acid components of non ribosomal peptides
Primordial amino acid components of non-ribosomal peptides

β-alanine, α-aminobutyric acid,β-aminobutyricacid, γ-amino-butyric acid, α-amino-isobutyric acid, α,γ-diaminobutyric acid, α,β-diaminopropionic acid, α-hydroxy-γ-aminobutyric acid, isoserine, N-methylalanine, 3-methylglutamic acid, isovaline, norvaline, sarcosine

etc…

diketopiperazines potential catalysts and signals
Diketopiperazines: potential catalysts and signals

There are at least three mechanisms for the synthesis of DKPs!

targets binding sites of bioactive small molecules and macromolecular evolution
Targets (binding sites) of bioactive small molecules and macromolecular evolution
  • Transcription (rifampicin, streptolydigin)
  • Replication (novobiocin)
  • *Translation (tetracycline, streptomycin, chloramphenicol)
  • Cell wall synthesis (penicillin, vancomycin)
  • Metabolic pathways (azaserine)

Did bioactive small molecule interactions play roles in the evolution of cellular macromolecules such as ribosomes and polymerases?

slide18

Antibiotic Binding Sites (Receptors)

on Prokaryote Ribosomes

30S

50S

This2.5 mD macromolecule is the sensor/receptor for many signals.

slide19

A model for the chronological evolution of the ribosome based

on accretion from existing structures.

(Note: no interactions with small molecules!)

Harish and Caetano-Anolles (2012)

PLoS ONE 7(3): e32776.

doi:10.1371/journal.pone.0032776

slide21

KEEP CLEAN

Wash your hands!

Tantalus Mountains,BC

slide22

THE FUTURE!

PNAS 2012,in press.