The increasing prevalence of antibiotic resistance in bacterial pathogens has 
renewed focus on natural products with antimicrobial properties. Lantibiotics 
are ribosomally synthesized peptide antibiotics that are posttranslationally 
modified to introduce (methyl)lanthionine bridges. Actinomycetes are renowned 
for their ability to produce a large variety of antibiotics, many with clinical 
applications, but are known to make only a few lantibiotics. One such compound 
is planosporicin produced by Planomonospora alba, which inhibits cell wall 
biosynthesis in Gram-positive pathogens. Planosporicin is a type AI lantibiotic 
structurally similar to those which bind lipid II, the immediate precursor for 
cell wall biosynthesis. The gene cluster responsible for planosporicin 
biosynthesis was identified by genome mining and subsequently isolated from a P. 
alba cosmid library. A minimal cluster of 15 genes sufficient for planosporicin 
production was defined by heterologous expression in Nonomuraea sp. strain ATCC 
39727, while deletion of the gene encoding the precursor peptide from P. alba, 
which abolished planosporicin production, was also used to confirm the identity 
of the gene cluster. Deletion of genes encoding likely biosynthetic enzymes 
identified through bioinformatic analysis revealed that they, too, are essential 
for planosporicin production in the native host. Reverse transcription-PCR 
(RT-PCR) analysis indicated that the planosporicin gene cluster is transcribed 
in three operons. Expression of one of these, pspEF, which encodes an ABC 
transporter, in Streptomyces coelicolor A3(2) conferred some degree of 
planosporicin resistance on the heterologous host. The inability to delete these 
genes from P. alba suggests that they play an essential role in immunity in the 
natural producer.