Biosynthesis of Novel Statins by Combining Heterologous Genes from Xylaria and Aspergillus | Zendy

Hiroya Itoh | Zendy; Makoto Matsui | Zendy; Yuki Miyamura | Zendy; Itaru Takeda | Zendy; Jun Ishii | Zendy; Toshitaka Kumagai | Zendy; Masayuki Machida | Zendy; Takahiro Shibata | Zendy; Masanori Arita | Zendy

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Biosynthesis of Novel Statins by Combining Heterologous Genes from Xylaria and Aspergillus

Author(s) -

Hiroya Itoh,

Makoto Matsui,

Yuki Miyamura,

Itaru Takeda,

Jun Ishii,

Toshitaka Kumagai,

Masayuki Machida,

Takahiro Shibata,

Masanori Arita

Publication year - 2018

Publication title -

acs synthetic biology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.156

H-Index - 66

ISSN - 2161-5063

DOI - 10.1021/acssynbio.8b00392

Subject(s) - aspergillus terreus , gene , polyketide , biology , heterologous , heterologous expression , biosynthesis , lovastatin , computational biology , genetics , biochemistry , recombinant dna , cholesterol

For many secondary metabolites, heterologous synthesis is the definitive step to determine their required biosynthetic genes. Using a multivector expression system in Saccharomyces cerevisiae, we reconstituted not only two natural statins from two fungal species, i.e., lovastatin from Aspergillus terreus and FR901512 from Xylaria grammica, but also new statin structures by mixing their genes. Combinatorial gene exchange experiments revealed the functional promiscuity of two polyketide synthases in A. terreus, lovB, and lovF; they could synthesize FR901512 with Xylaria genes. Key structure determinants of statins are essential accessory genes that are irreplaceable across species.

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