論文 - 詳細
| RRC ID | 84561 |
|---|---|
| 著者 | Kudo F, Tsuboi K, Ikezaki M, Nagayama D, Kawamura K, Ando T, Miyanaga A, Eguchi T. |
| タイトル | The Post-Polyketide Synthase Modification Mechanism in Hitachimycin Biosynthesis. |
| ジャーナル | Chembiochem |
| Abstract |
Hitachimycin is a bicyclic macrolactam antibiotic with (S)-β-phenylalanine (β-Phe) at the starter position of the polyketide skeleton. While the enzymes that recognize β-amino acids, modify the aminoacyl groups, and transfer the resultant dipeptide groups to the acyl carrier protein domains of polyketide synthases (PKSs) have been studied extensively, the post-PKS modification mechanism responsible for constructing the unique bicyclic structure of hitachimycin remains elusive. In this study, we first inactivated six genes encoding putative post-PKS modification enzymes, namely hitM1 to hitM6, in Streptomyces scabrisporus to determine their involvement in hitachimycin biosynthesis. The ΔhitM4 strain accumulated an all-trans-2,4,6,8,18-pentaene macrolactam, which was confirmed as a true intermediate in hitachimycin biosynthesis by cellular feeding experiments, and appears to be the initial intermediate in the post-PKS modification pathway. The ΔhitM1 strain accumulated 10-O-demethyl-10-oxohitachimycin (M1-A). In enzymatic experiments, M1-A was reduced by the NAD(P)H-dependent reductase HitM1 in the presence of NADPH. The product of the reaction catalyzed by HitM1 was converted to hitachimycin by the methyltransferase HitM6. We thus propose a plausible post-PKS modification mechanism for the biosynthesis of hitachimycin. |
| 巻・号 | 25(16) |
| ページ | e202400405 |
| 公開日 | 2024-8-19 |
| DOI | 10.1002/cbic.202400405 |
| PMID | 38849317 |
| MeSH | Anti-Bacterial Agents / biosynthesis Anti-Bacterial Agents / chemistry Anti-Bacterial Agents / metabolism Lactams, Macrocyclic / chemistry Lactams, Macrocyclic / metabolism Molecular Structure Polyketide Synthases* / genetics Polyketide Synthases* / metabolism Streptomyces* / enzymology Streptomyces* / genetics Streptomyces* / metabolism |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 一般微生物 | JCM11712 |