Genomic Analysis of Fungal Species No.11243 Mutant Strains Provides Insights into the Relationship between Mutations and High Productivity
Makoto Matsui
Biotechnology Labs, Astellas Pharma Inc., Japan
Tatsuya Yokoyama
Biotechnology Labs, Astellas Pharma Inc., Japan
Toshitaka Kumagai
Fermlab Inc., Japan
Kaoru Nemoto
Technology Research Association of Highly Efficient Gene Design (TRAHED), Japan
Goro Terai
Advanced Technology Research and Development Institute, INTEC Inc., Japan
Masayuki Machida
Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Japan
Takashi Shibata
Biotechnology Labs, Astellas Pharma Inc., Japan
Sachiyo Aburatani
Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Japan
*Author to whom correspondence should be addressed.
Abstract
Aims: FR901469 is a novel antifungal antibiotic produced by fungal species No.11243. Although we have several FR901469 high-producing mutant strains, the mechanism of high productivity is unclear. This study aims to unravel the relationship between mutations and FR901469 productivity.
Methodology: We performed genome sequence analysis of mutant strains and detected mutated genes. Subsequently, we classified mutated genes into functional categories and searched the categories in which mutated genes were accumulated as generations progressed.
Results: We found that genome regions of two scaffolds were amplified and one of those contained putative FR901469 biosynthesis gene cluster. Moreover, we detected totally 396 mutated genes from 14 mutant strains and the genes within the “Replication, recombination and repair”, “Signal transduction mechanisms” and “Transcription” categories accumulated this mutation.
Conclusion: Our study suggests that productivity improvement occurs via the following two mechanisms: the amplification of putative FR901469 biosynthesis gene cluster and mutations of genes categorized as “Replication, recombination and repair”, “Signal transduction mechanisms” and “Transcription”.
Keywords: FR901469, fungal sp. No.11243, genomic analysis, mutation