Transfer of Secondary Metabolite Gene Clusters: Assembly and Reorganization of the β-Lactam Gene Cluster from Bacteria to Fungi and Arthropods

  • J. F. MartínEmail author
  • P. Liras


Filamentous fungi are able to produce a wide array of secondary metabolites with important biological and medical activities. The biosynthesis of secondary metabolites is encoded by gene clusters that include structural, regulatory and transport genes. Complete sets of genes are transferred by HGT from bacteria to fungi and to higher eukaryotes. In addition, genes have been laterally transferred by LGT between phylogenetically distant fungi.

Many of these HGTs involve genes derived from bacteria that have been modified in fungi by incorporating new genes of eukaryote origin. Important examples of HGT from bacteria to fungi include the transfer of the 6-methylsalicylic acid gene cluster and the three-gene cluster for the reduction of nitrate to ammonia. Examples of lateral transfer of NRPS and PKS gene clusters are discussed. The evolution of β-lactam gene clusters constitutes a paradigmatic example of the assembly, transfer, modification and conservation of gene clusters. In the Eurotiales (Penicillium/Aspergillus), the pcbAB and pcbC genes were integrated next to a three intron-containing gene, penDE, encoding an acyltransferase. In the Hypocreales (Acremonium/Kallichroma/Pochonia), a larger gene cluster was assembled that contains also the bifunctional isopenicillin N expandase-hydroxylase gene, which derives from homologous genes in bacteria. Since the bidirectional divergent arrangement of pcbAB-pcbC genes is common to all fungi, in contrast to the head to tail organization of these genes in all bacteria, we conclude that a major reorganization of these two genes took place during the initial transfer from bacteria to a β-lactam ancestor in fungi. The phylogenetic studies indicate that a single ancient HGT event took place from Gram-negative bacteria followed by a lateral transfer from a receptor fungus from the Hypocreales order to other fungi. Interestingly, the first two genes of the penicillin-cephalosporin gene cluster have been found in the arthropod Folsomia candida. The phylogenetic tree supports the conclusion that these β-lactam genes were transferred to F. candida in an early separated event.


Horizontal gene transfer (HGT) Lateral gene transfer (LGT) Secondary metabolites Gene clusters origin LGT in fungi β-Lactam gene cluster β-Lactam cluster reorganization β-Lactam genes in arthropods 


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Authors and Affiliations

  1. 1.Section Microbiology, Department of Molecular BiologyUniversity of LeónLeónSpain

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