Introduction Flashcards
What is a natural product?
made with enzymes –
much more selective. Bigger range of molecules
Example of Natural Products (4)
Penicillin, Taxol, Vincristine, Cyclosporin
Natural Products as primary metabolites
essential to the organisms (amino acids, nucleotides, sugars)
common across most organisms
involved in growth, reproduction and development
do not participate in defence
Natural Products as secondary metabolites
not essential for survival
unique to an organism or a group of organisms
not involved in growth, reproduction and development
important for defence and confer an advantage to the organism
What organisms can produce natural products and why?
Prokaryotic - bacteria (including cyanobacteria), archaea, viruses
Eukaryotic - algae, fungi/yeasts/moulds, plants, animals
Why can the organisms produce natural products?
Defence: NPs can kill, harm and repel competitors (e.g. symbiotic relationship with plants and fungi for defence)
Protection: against UV radiation and other environmental stresses
Attraction: lure in other beneficial microbes or animals (e.g. aromatic - molecule allows plant to select for specific insect)
Nutrient uptake or release/detoxification: siderophores and metal chelators (e.g. bacteria in soil help plant survive by providing molecule to help it survive - metal)
stimulating, sensing/signalling + more
Leaf-cutter ants microbiome
ants forage on leaves + fungus is on leaves
fungus eats leaves -> ants eat fungus
produce chemicals to defend from pathogen
molecule/chemicals alters ant behaviour -> no longer tidying nest -> pathogen can set in
pathogen Ralstonia solanacearum produces lipopeptide called ralsolamycin - in high quantity kills the fungal competitors (antifungal) - in small quantities induces chlamydospore formation - used to colonise fungal tissue to survive in the cold - hitchhikers
Application of NPs in Health
antimicrobial resistance - 1.4M direct deaths & 4.95M indirect death in 2019 (WHO)
new diseases
cancer
35% drugs are or are derived from NPs
NPs have an array of bioactive properties
More organisms to isolate and test
Application of NPs in Agriculture
feeding the planet
new diseases
find new pesticides (P), herbicides (H), antifungals (A)
NPs - (P) 39% (32% sales), (A) 17% (35% sales) and (H) 10% (12% sales)
Application of NPs in Industrial Pollution
pollution
chemical waste
non-sustainable products
green chemistry - using microbiomes and enzymes to make complex molecules
use NP as green dyes for clothing
Penicillin - Fleming
1928 Fleming unexpected discovery of penicillin (beginning of modern antibiotic era)
Fleming began work with mould: Penicillium notatum
demonstrated ability of fungus to kill many pathogenic bacteria + showed it possessed little toxicity to humans
could not isolate an dpurify penicillin as stable compound so abandoned work on P. notatus 1934
Penicillin - the reoccurrence of penicillin
1938 - Howard Florey and Ernst Chain from Oxford Uni managed to isolate enough penicillin to cure a 15-year-old boy of post-operative infection
years later identified much better producing strain: Penicillium chrysogenum, from moldy cantaloupe melon
Dorothy Crowfoot Hodgkin solved structure in 1945
estimated over 500 million lives saved by penicillin
Nystatin
Elizabeth Lee Hazen + Rachel Brown discovered first antifungal in 1950
Effective against Candida infection and prevent fungal infection
Isolated from bacterium Streptomyces noursei
No. estimated death from fungal disease in 2021 approx 7000 in USA
250,000 - 700,000 cases of invasive candidiasis per year
direct medical costs estimated at $6.7 to $7.5 billion yearly
Taxol
discovered by Arthur Barclay - first antifungal in 1962
anticancer agent - antimicrotubule agent
isolated from bark of Taxus brevifolia (Pacific yew) tree
considered by WHO one of essential medicines
best-selling cancer drug manufactured
Mevastatin & Lovastatin
Mevastatin discovered by Akira Endo 1970s from Penicillium citrinum
Lovastatin discovered from Aspergillus terreus 1982 - produced by Pleurotus ostreatus (oyster mushroom) - less side effects
treatment of high blood cholesterol and reduces cardiovascular disease - HMG-CoA reductase inhibitors
global statins market size reached US$ 15 Billion
