CO2 + H2O

NATURAL PRODUCTS

PHOTOSYNTHESIS

glucose & other carbohydrate polysaccharides

nucleosides RNA & DNA

PPP
GLYCOLYSIS
lignans, coumarins

phosphoenol pyruvate SHIKIMATE

aromatic AA’s proteins, enzymes, alkaloids

pyruvate
terpenoids, steroids,
mevalonic acid
carotenoids

acetyl coA
lipids, polyketides polyphenols, prostaglandins

TCA aliphatic AA’s proteins, enzymes, alkaloids

POLYKETIDES
have alternating carbonyl
& methylene groups
 Sources

Microbes Marine Plants Insects

Bacteria & Mollusks, Flowers, Beetles
Fungi sponges, algae, Fruiting Bodies,
crinoids Berries, Bark,
Seeds & Stems
Macrolides

erythromycin A O
OH
similar in antimicrobial
spectrum to penicillin HO O desosamine

an antibiotic for respiratory HO

tract infection
O
O dadinose

O
Macrolides

clarithromycin A
used to treat pharyngitis, tonsillitis, acute
maxillary sinusitis, acute bacterial
exacerbation of chronic bronchitis,
pneumonia
Macrolides

azithromycin
used to treat or prevent certain bacterial infections, most often
those causing middle ear infections, strep throat, pneumonia,
typhoid, bronchitis and sinusitis
prevents bacteria from growing by interfering with their protein
synthesis; binds to the 50S subunit of the bacterial ribosome,
and thus inhibits translation of mRNA
brand names: Zithromax, Azithrocin, Zmax, Azin, Zedd,
Azocam, Penalox, Azi-Once, Zeto, Azyth
side-effect: diarrhea (5%), nausea (3%), abdominal pain (3%),
and vomiting
Macrolides

avermectin
generated as fermentation products by Streptomyces
avermitilis, a soil actinomycete
has potent anthelmintic and insecticidal properties
Tetracycline

• from Streptomyces
• a protein synthesis inhibitor
Tetracycline

Doxycycline
used to treat Lyme disease, chronic prostatitis,
sinusitis, pelvic inflammatory disease, acne,
rosacea,and rickettsial infections
used in prophylaxis against malaria
used in the treatment and prophylaxis of anthrax
(caused by Bacillus anthracis) and leptospirosis
brand names: Vibramycin Monodox, Microdox,
Periostat, Vibra-Tabs, Oracea, Doryx,Vibrox,
Adoxa, Doxyhexal, Doxylin, Doxoral, Doxy-1',
Atridox
Ansamycins

• has antimicrobial activity against many gram-positive and some

gram-negative bacteria

rifamycin
effective against mycobacteria, and are therefore used to treat
tuberculosis, leprosy, and mycobacterium avium complex
(MAC) infections
brand names: Rifampicin or Rifampin, Rifabutin, Rifapentine,
Rifaximin
Ansamycins

• has antimicrobial activity against many gram-positive and some

gram-negative bacteria

geldanamycin
a benzoquinone ansamycin antibiotic that inhibits the function
of Hsp90 (Heat Shock Protein 90)
induces the degradation of proteins that are mutated in tumor
cells such as v-Src, Bcr-Abl and p53 preferentially over their
normal cellular counterparts
side-effect: hepatotoxic
Other important polyketides
Lovastatin
• used in combination with diet, weight-loss, and exercise
for lowering cholesterol (hypolipidemic agent) in those
with hypercholesterolemia to reduce risk of cardiovascular
disease
• a naturally occurring drug found in food such as oyster
mushrooms and red yeast rice
• brand names: Mevacor, Advicor, Altocor, Altoprev,
Deterrent
Acetogenins
Acetogenins

• found in plants of the family Annonaceae (custard apple family)

• characterized by linear 32- or 34-carbon chains

Annonacin
a chemical found in some fruits such as the custard
apple and Sour Sop
antitumor, pesticidal, antimalarial, anthelmintic,
piscicidal, antiviral, and antimicrobial
Acetogenins

• found in plants of the family Annonaceae (custard apple family)

• characterized by linear 32- or 34-carbon chains

Bullatacin
a bis(tetrahydrofuranoid)
fatty acid lactone
Acetogenins

• found in plants of the family Annonaceae (custard apple family)

• characterized by linear 32- or 34-carbon chains

Uvaricin
has potent anti-cancer activity
Other important polyketides
Aflatoxin
• carcinogen from Aspergillus,; among the most carcinogenic substances known
• exposure produces acute hepatic necrosis, resulting later in cirrhosis, and/or
carcinoma of the liver
Other important polyketides
Usnic acid
• a bitter yellow solid found in lichens
• used in cosmetics, perfumery and medicine
• a potent antibiotic against Gram-positive bacteria
• also exhibits antiviral, antiprotozoal, antimitotic, anti-
inflammatory and analgesic activity
• used as preservative, anti-herbivore, anti-insect
• used as ingredient in creams, powders, toothpaste,
mouthwash, deodorants and sunscreen products
Other important polyketides
Anthracimycin
• derived from marine actinobacteria and has shown
significant activity against Bacillus anthracis, the bacteria
that causes anthrax
POLYKETIDES

poly--keto-acyl-CoA
- from condensation of acetyl-CoA and malonyl CoA

O O
CH3 C + O- C CH2 C S CoA
S CoA
O
acetyl-CoA malonyl-CoA
O

CH3 C CH2 C S CoA

O O n(malonyl-CoA)

CH3 C CH2 C CH2 C SCoA

O n