Selective reminiscences of beta-lactam antibiotics: early research on penicillin and cephalosporins

Bioessays. 1990 Dec;12(12):601-6. doi: 10.1002/bies.950121208.


The discovery, made in Oxford, that crude penicillin could cure systemic and life-threatening bacterial infections was followed by attempts to purify penicillin, to determine its structure and then to produce it by total chemical synthesis. The beta-lactam structure of the molecule, first proposed in October 1943, was a source of controversy until 1945. However, no useful chemical synthesis was achieved and fermentation became the commercial source of the antibiotic. In 1953, one of the products of a Cephalosporium sp. from Sardinia was shown to be a new and hydrophilic penicillin (penicillin N). This was contaminated with a substance having the same side-chain but a characteristic absorption spectrum. The latter, cephalosporin C, showed antibacterial activity but was not inactivated by a penicillinase. The determination of its beta-lactam structure and isolation of its nucleus enabled pharmaceutical companies to produce many semisynthetic cephalosporins. A new tripeptide was later found to be an intermediate in the biosynthesis of both penicillin N and cephalosporin C, and this was followed by the complete elucidation of the biosynthetic pathways leading to these compounds and to benzylpenicillin.

Publication types

  • Biography
  • Historical Article

MeSH terms

  • Cephalosporins / chemistry
  • Cephalosporins / history*
  • England
  • History, 20th Century
  • Penicillins / chemistry
  • Penicillins / history*


  • Cephalosporins
  • Penicillins

Personal name as subject

  • E Abraham