“Lantibiotics are antibiotic molecules produced by soil bacteria, and we are studying probably the most potent one known, microbisporicin, which is active against many different pathogens,” said Professor Mervyn Bibb from the John Innes Centre, co-author on the paper to be published in PNAS. "Our study has allowed us to understand how the antibiotic is made by a bacterium that was first isolated from Indonesian soil.  Now we can engineer the bacterium to make similar but better molecules, and lots of them.”

“We can take rational approaches to improve its pharmacological properties, such as its stability in the blood stream and how it distributes into tissues.”

The producing bacterium, Microbispora corallina, is difficult to work. It grows very slowly and no tools existed for its genetic manipulation. PhD student Lucy Foulston developed the tools herself. She then took advantage of new developments in genome sequencing to identify and then isolate the M. corallina gene cluster responsible for microbisporicin production.

This allowed her to analyse how the bacterium makes the molecule and the functions of the genes involved. Notably, she was able to identify the genes responsible for giving microbisporicin some of its unique features.

The antibiotic molecule binds to a well established target in the pathogenic bacteria it kills, and as yet there are no signs of resistance towards it. Microbisporicin is very effective at killing disease-causing bacteria, including Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant pathogens.

“This molecule is already in late preclinical-phase trials and in animal models has shown to be more effective than the current drugs of last resort, linezolid and vancomycin,” said Professor Bibb. “We believe this study will make a major contribution to the future clinical development of this exciting antibiotic, and that derivatives that can be made using the knowledge and technology that we have developed.”

The John Innes Centre is an institute of the Biotechnology & Biological Sciences Research Council (BBSRC) who funded the research.

Already one patent out on two antibiotics
In April 2003, a US patent No: 6551591 was granted for antibiotics from microbispora with a new strain of Microbispora corallina which had been filed in 2001. It was awarded to May D Lee (Los Altos, CA) and assigned to Essential Therapeutics Inc, (Mountain View, CA) 

That invention related to two antibiotics designated MF-BA-1768.alpha..sub.1 and MF-BA-1768.beta..sub.1, to their production by fermentation, methods for their recovery and concentration from fermentation broth, as well as processes for their purification.

It included within its scope the antibiotics in dilute form, in crude concentrates, in complexes of various or all components, and in pure form as individual compounds. It also includes a new strain of Microbispora corallina, which produces the compounds identified by the DNA sequence that codes for its partial 16S rRNA sequence and by its nutrient utilisation pattern.

The chemical structures of the new antibiotics are presently unknown but four potential structural features have been deduced based on partial 2-D NMR data including .sup.1 H--.sup.1 H correlation (COSY) and .sup.1 H--.sup.13 C correlation (HMQC).

Compounds are characterised by their physical and chemical properties including UV, IR, and .sup.1 H NMR spectra. Their molecular weights were determined by ESI-FTMS.