This document discusses past and present research on antibiotic-producing actinomycetes. It covers key discoveries from the 1940s-1960s, including antibiotics like penicillin, tetracyclines, and cephalosporins. Current research focuses on genomics, combinatorial chemistry, and high-throughput screening, which have not yielded new antibiotics. The document advocates returning to whole-cell screening of actinomycete broths, which more directly tests for antibiotic activity. It also describes using macrodroplets to simplify actinomycete culturing and screening against drug-resistant E. coli to identify promising new antibiotic candidates. Challenges with metagenomic approaches are noted.

1. A Review of Antibiotic producing
Actinomycetes Research past and present
B.S.Kalyani
Department of Applied Life Sciences
Dantuluri Narayana Raju College
Bhimavaram
Andhra Pradesh

2. • The Two faced Roman god “ Janus” could see
both forward and backward simultaneously
• In Novel antibiotic discovery from
Actinomycetes “Janus effect” can be described as
the ability to reflect furthest back and also to plan
ahead effectively
• Today we are in the cusp stage of Post antibiotic
era

3. • Antibiotic Research from Alexander Flemings
discovery of Penicillin to our present day has been an
exciting and continously developing adventure.
• During the 1940s and early 50s almost all the
important antibacterial antibiotics
• Tetracyclines,Cephalosporins,Aminoglycosides,
• Macrolides have been discovered
• More than one half of the antibiotic principles were
produced by Actinomycetes in particul streptomyces
species alone in 50s and 60s

4. Streptomyces
• The most common genus of Actinomycetes is
Streptomyces till date about 500 species of
Streptomyces have been described.
• Their antibiotics were effective against Bacteria and Fungi.
• Later Research lead to the isolation of many bioactive
secondary metabolites from Actinomycetes
1) Anti tumor agents
2)Immunosuppressive agents

5. More Bioactive Metabolites of Actinomycetes
• Antioxidants
• Antialgal
• Antihelmenthic
• Antimalarial
• Antiinflammatory
• The list is endless…………

6. Reflecting upon the Past
Most antibiotics in clinical use in the past were direct
natural products or semisynthetic derivatives from
Actinomycetes or Fungi
Erythromycin,Vancomycin,Cephalosporin and
Tetracycline were discovered through whole cell
antibacterial screening procedures.
At present this traditional method of identifying
antibiotics by screening extracts from Actinomycetes
against Pathogens is no longer considered glitzy
science

7. Present Scenario
Actinomycete derived antimicrobial research is
focused on approaches of Target based antibiotic
discovery using Bacterial Genomics,
combinatorial chemistry and high throughput
screening
These approaches have not yielded any antibiotics
approved for clinical use and the prospects for its
success are not encouraging

8. What is High Through put Invitro Screening
It depends on finding activity against a particular
hypothetical target.
It starts with a search for chemicals in Libraries
that can inhibit a single enzyme from a pathogen.
If a chemical shows promising activity ,then
Medicinal chemists modify it to ensure appropriate
levels of penetration,stability,toxicity,tissue
distribution and elimination from the body

9. Whole cell Screening of broths from
Actinomycetes
This approach quickly leads to biologically
active compounds because the broths are screened
against potentially druggable targets
It also tests for wether candidate molecules
penetrate outer barriers of cells and are active
against pathogens
This difference from highthroughput invitro
screening makes whole cell screening more
logical.

10. Pharmaceutical companies apathy
 Many Stopped relying on low technology logic
 Began to apply genomics ,combinatorial
chemistry,target based screening to all
therapeutic areas,including the search for novel
antimicrobial products.
 Companies today understand what happens
when high technology hypothetical approaches
are not specifically validated

11. Macrodroplets simplify,miniaturize screening for
novel Actinomycete Antibiotics
• We can screen more than 10 separate
Actinomycetes per year using simplified steps
for isolating and growing them
• Spores are packed into calcium alginate
macrodroplet beads that are 2mm in diameter
• Contain nutrient media plus a cocktail of
naladixic acid ,trimethoprim,nystatin and
cyclohexamide to inhibit fungi and
nonactinomycete bacteria

12. Screening to exclude common
Antibiotics
• Actinomycete spores germinate,mycelia
grow,differentiate and produce secondary
metabolites in the beads
• This technique allows us at present to screen
Millions of Actinomycete spores per year with
minimal Automation
• Because more than 60% of known Actinomycete
antibiotics are active against Gram positive
Bacteria, using E.coli simplified the screening

13. E.coli genetics are an advantage
• Inserting multiple resistance genes into the
E.coli chromosome made the test strain easy to
maintain
• Reduced the overall hit rate to less than 0.1%
• So many known antibiotics were excluded so
this approach made subsequent structural
analysis of promising antimicrobial candidates
more manageable

14. Problems applying Metagenomics when
searching for Novel antibiotics
• Metagenomics are useful for microbes that
cannot be easily cultivated
• No practical success in finding new antibiotics
• There are technical limits
• No guarantee that uncultivable microbes will
give us novel antibiotics