Aspects of Marine Biotechnology - University of Aberdeen

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12 Φεβ 2013 (πριν από 4 χρόνια και 4 μήνες)

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Aspects of Marine Biodiscovery


Professor Marcel Jaspars, Marine Biodiscovery Centre, University of Aberdeen, Scotland, UK.
m.jaspars@abdn.ac.uk


1.)

History.

This topic will cover the historical uses of natural res
ources, mainly with medical applications.

a.

Traditional medicine


herbals

b.

Currently used medicines from terrestrial plants and microorganisms.

c.

From cocaine to the dentist


the development of safe local anaesthetics.

d.

Ethnobotany versus bioprospecting/biodis
covery


References
:

Mann,
Murder, Magic and Medicine,
OUP, 2000;
J Nat Prod

2003
,
66
, 1022;
Sneader,
Drug
Prototypes and Their Exploitation,
Wiley 1996.


2.)

Secondary Metabolism
. This topic will cover the differences between primary and secondary metabolism,
and the reasons why they are produced.

a.

Defining secondary metabolites

b.

The
link

between primary and secondary metabolism

c.

The role of secondary metabolites & why they are produced.

d.

Privileged

structures and protein folds.


References
:

Mann,
Chemical Aspects
of Biosynthesis
, OUP 1994, Williams,
J Nat Prod

1989
,
52
, 1189
;
Waldmann,
Angew Chem

2002
,
41
, 2878; Quinn
J Nat Prod

2006
,
69
, 14;
J Am Chem Soc

2000
,
122
, 9939;
J Med
Chem

2003
,
46
, 2917;


3.)

Natural Versus Synthetic Compounds in Drug Discovery
. This topic

will compare the value of synthetic
and natural compounds in modern drug discovery.

a.

Challenges to modern drug development

b.

Lipinski’s rules applied to natural and synthetic compounds

c.

Structural diversity

d.

Screening natural versus synthetic compounds

e.

When to

use natural products


References
:
J Health Econ

2003,
22
, 151;
Nat Rev Drug Disc

2004
,
3
, 711; Lee,
J Comb Chem
,
2001
,
3
, 284;
Feher,
J Chem Inf Comp Sci
,
2003
,
43
, 218;
Urbaniak, Bioorg Med Chem Lett
,
2006
,
16
,
5744; Nature Insight
Chemical Space
,
Nature

16 Dec
2004
, Vol 432; Baker in
Biodiversity
, RSC,
2000
, p 66
; Bauer,
Current Opinion in
Chemical Biology

2010
,
14
, 308
; Lipinski,
Advanced Drug Delivery Reviews
,

2001
,

46
,

3


4.)

Practical and Legal Aspects in Biodiscovery
.

a.

Flowchart of the discovery process

b.

Implications of the Convention on Biodiversity

and the Nagoya Protocol

c.

United Nations Convention on the Laws of the Sea

d.

Collection and preservation of specimens

e.

The importance of taxonomy

f.

Extraction of specimens

g.

Screening protocols & bioassay guided isolat
ion

h.

Purification

methods

i.

Dereplication

j.

Structure determination


References:

Nature Insight


Biodiversity
,
Nature,
2000,
405,
207
-
253;
J. Nat. Prod.
1995,
58,
1325
; ten Kate and
Laird,
The Commercial use of Biodiversity,
Earthscan 1999;

Nature

1998
,
391
,
12 Feb, p629;
Kingsford and
Battershill,
Studying Temperate Environments
, CRC Press 1998; Houghton & Raman,
Laboratory Handbook for
the Fractionation of Natural Extracts,
Chapman & Hall, 1998;
Houssen & Jaspars in
Natural Products Isolation
,
Humana,
2005;
Jaspars
Nat Prod Rep

1999
,
16
, 241;


5.)

The Marine Environment as a Unique Resource

a.

Conditions in the marine environment

b.

Nutrient limitations

c.

Phyletic diversity & forgotten phyla

d.

Marine microbial diversity

e.

Chemistry in extreme environments (deep/cold)


Refer
ences:

Pietra,
Biodiversity and Natural Product Diversity
,
Schneider,
Nat Prod Rep
.
2008
,
25
, 892
;
Tetr
ahedron Books, 2002
;
Skropeta D.,
Nat. Prod. Rep.
,
2008
,
25
, 1131
-
1166;
Baker
Nat. Prod. Rep
.
2007
,
24
,
774
;
Lozupone
Proc. Natl. Acad. Sci. U.S.A.

2007
,

104
, 11436
;
Jørgensen

Nat Rev Microbiology
,
2007
,
5
, 770
; Kong,
Drug Discovery Today
,
2010
,
15
, 884
.


6.)

The Marine Natural Product Pipeline
. This will consist of case studies of compounds that have made it
to the clinic from marine sources

a.

Prialt/Ziconotide

against neuropathic pain

b.

Anti
-
cancer activity by phylum

c.

AraC and AraA as anti
-
cancer agents

d.

Ecteinascidin 743/Yondelis/Trabectidin for soft tissue sarcoma
.

e.

Salinosporamide as an example of a marine microbial natural product

f.

Compounds in trials

g.

Compounds
n
o longer in

trials


References:

Newman
International Oncology Updates:
Recent progress of natural

marine products,
p19,
2008;

Molinski
Nature Reviews Drug Discovery
,
2009
,
8
, 69
-
85
,
Butler,

Nat. Prod.
Rep.
,

2008
,

25
, 475


7.)

Developing Marine Natural Products



The Supply Issue
.
Bringing marine natural products to the
market has been hampered by lack of a sustainable supply. These case studies show how these barriers can
be overcome.

a.

Recollection


halichondrin B

b.

Aquaculture economics for bryostatin
-
1 and ecte
inascidin 743

c.

Total synthesis


discodermolide

d.

Analogue synthesis

e.

Semi
-
synthesis


ecteinascidin 743

f.

Tissue culture


avarol

g.

Symbiont culture


manzamine

h.

Marine microbial culture


salinisporamide

i.

Heterologous expression
-

patellamide


References:

Chem Eng

News
, Oct 13,
2003
, p77;
Nat Rev Drug Disc,

2005
,
4
, 206
;
Cuevas and Francesch,
Nat.
Prod. Rep
.
2009

in press; Hill, Hamann, Peraud & Kasanah Patent WO 2004/013297 A2; Müller
J. Nat. Prod

2000
,
63
, 1077; Long
et al ChemBioChem

2005
,
6
, 1760;
Stach
Trends
in Microbiology
,
2007
,
15
, 491


8.)

Other Applications

of Marine Bioresources.

Medical applications are not the only high value
applications for marine bioresources. Other applications are:

a.

In aquaculture (
eg

carotenoids)

b.

Antifoulants

c.

Biofilm inhibitors (bromi
nated furanones)

d.

Novel enzymes (shrimp alkaline phosphatase)

e.

Tissue replacement (sponge collagen, coral in bone replacement)

f.

In foods (alginates)

g.

Nutraceuticals (EPA/DHA, glucosamine.

h.

Research tools


References:
Realising the Potential of Marine Biotechnol
ogy


Challenges and Opportunities, Michael J. Allen and
Marcel Jaspars,
Industrial Biotechnology,
2009
,
5
, 77


9.)

Policy



see
European Science Foundation’s Marine Board
position paper

“Marine Biotechnology


A
European Strategy”