Week-2: Murphy

Question 1

What inspired pharma to invest in microbial NP discovery (1930-1950)

Answer 1

• WW2
• death toll from infection
• 1929 Alexander Fleming [pencillin]
• dicovery that microbes coevolve and can use chemistry to fight one and other
• led to Golden Age of NP

Question 2

Factors that led Pharma to divest from NP drug discovery (1960-2000)

Answer 2

• Sucess rate went down
• NP research requires large team & is $$$
• HTS meant more samples and faster but was better for synthetic libraries
• Pharma divest and Universities take over

Question 3

Methodologies/straegies that drive NP drug discovery in moder era (2000-present)

Answer 3

• Exploration of New NP sources
  ** Novel Chemical Scaffolds **
  ** Unique mechanisms of Action**
  ** New Drug Target**
  “understudied” microbial taxa – of a 100 phyla only 5 phyla are heavily studied and the source of all NP drugs
• Development of New Methodology
  Access/exploit genetic information
  Process/analyze large data sets

*Enhanced Analytical techniques HPLC (mid-late 1970s), UPLC, MS, MS/MS (for dereplication)
*Cost of gene sequency lowered significantly making it more accessible (BGCs)
*Development of bioinformatics tools: GNPS, MIBiG, & DeepSat

  - NAtlas 
  - Genome Taxonomy Database