Abstract

BackgroundDue to the importance of Penicillium chrysogenum holding in medicine, the genome of low-penicillin producing laboratorial strain Wisconsin54-1255 had been sequenced and fully annotated. Through classical mutagenesis of Wisconsin54-1255, product titers and productivities of penicillin have dramatically increased, but what underlying genome structural variations is still little known. Therefore, genome sequencing of a high-penicillin producing industrial strain is very meaningful.ResultsTo reveal more insights into the genome structural variations of high-penicillin producing strain, we sequenced an industrial strain P. chrysogenum NCPC10086. By whole genome comparative analysis, we observed a large number of mutations, insertions and deletions, and structural variations. There are 69 new genes that not exist in the genome sequence of Wisconsin54-1255 and some of them are involved in energy metabolism, nitrogen metabolism and glutathione metabolism. Most importantly, we discovered a 53.7 Kb "new shift fragment" in a seven copies of determinative penicillin biosynthesis cluster in NCPC10086 and the arrangement type of amplified region is unique. Moreover, we presented two large-scale translocations in NCPC10086, containing genes involved energy, nitrogen metabolism and peroxysome pathway. At last, we found some non-synonymous mutations in the genes participating in homogentisate pathway or working as regulators of penicillin biosynthesis.ConclusionsWe provided the first high-quality genome sequence of industrial high-penicillin strain of P. chrysogenum and carried out a comparative genome analysis with a low-producing experimental strain. The genomic variations we discovered are related with energy metabolism, nitrogen metabolism and so on. These findings demonstrate the potential information for insights into the high-penicillin yielding mechanism and metabolic engineering in the future.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-S1-S11) contains supplementary material, which is available to authorized users.

Highlights

  • Due to the importance of Penicillium chrysogenum holding in medicine, the genome of low-penicillin producing laboratorial strain Wisconsin54-1255 had been sequenced and fully annotated

  • There are 69 “new” genes that not exist in the genome sequence of Wisconsin54-1255 and some of them are involved in energy metabolism, nitrogen metabolism and glutathione metabolism

  • We found two large translocations in NCPC10086; one is a 266 Kb fragment in subtelomere transferred to centromere including genes regulating nitrogen metabolite repression; another is a 1,202 Kb fragment consists of a mitochondrial ADP/ATP carrier involved in energy metabolism and peroxin-2 gene involved in peroxysome pathway

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Summary

Introduction

Due to the importance of Penicillium chrysogenum holding in medicine, the genome of low-penicillin producing laboratorial strain Wisconsin54-1255 had been sequenced and fully annotated. Through classical mutagenesis of Wisconsin54-1255, product titers and productivities of penicillin have dramatically increased, but what underlying genome structural variations is still little known. Through classical mutagenesis and screening methods, product titers and productivities of penicillin have dramatically increased since Wisconsin54-1255 strain, but how lowpenicillin producer strain was transformed into an efficient producer through improvement is still challenging. Some significant structural variations (SVs) [8,9,13] and differential expression profiling [12,14,15] have been found in high-penicillin producing strains, little is known about the underlying whole genomic changes between low-producing laboratorial strain and high-producing industrial strain

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