Dataset Information

An Amidinohydrolase Provides the Missing Link in the Biosynthesis of Amino Marginolactone Antibiotics.

ABSTRACT: Desertomycin?A is an aminopolyol polyketide containing a macrolactone ring. We have proposed that desertomycin?A and similar compounds (marginolactones) are formed by polyketide synthases primed not with ?-aminobutanoyl-CoA but with 4-guanidinylbutanoyl-CoA, to avoid facile cyclization of the starter unit. This hypothesis requires that there be a final-stage de-amidination of the corresponding guanidino-substituted natural product, but no enzyme for such a process has been described. We have now identified candidate amidinohydrolase genes within the desertomycin and primycin clusters. Deletion of the putative desertomycin amidinohydrolase gene dstH in Streptomyces macronensis led to the accumulation of desertomycin?B, the guanidino form of the antibiotic. Also, purified DstH efficiently catalyzed the in?vitro conversion of desertomycin?B into the A form. Hence this amidinohydrolase furnishes the missing link in this proposed naturally evolved example of protective-group chemistry.

SUBMITTER: Hong H

PROVIDER: S-EPMC4737276 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An Amidinohydrolase Provides the Missing Link in the Biosynthesis of Amino Marginolactone Antibiotics.

Hong Hui H Samborskyy Markiyan M Lindner Frederick F Leadlay Peter F PF

Angewandte Chemie (International ed. in English) 20151202 3

Desertomycin A is an aminopolyol polyketide containing a macrolactone ring. We have proposed that desertomycin A and similar compounds (marginolactones) are formed by polyketide synthases primed not with γ-aminobutanoyl-CoA but with 4-guanidinylbutanoyl-CoA, to avoid facile cyclization of the starter unit. This hypothesis requires that there be a final-stage de-amidination of the corresponding guanidino-substituted natural product, but no enzyme for such a process has been described. We have now ...[more]

PMID: 26630438

Similar Datasets

Project description:The origin and deep evolution of retroviruses remain largely unclear. It has been proposed that retroviruses might have originated from a Ty3/Gypsy retrotransposon, but all known Ty3/Gypsy retrotransposons are only distantly related to retroviruses. Retroviruses and some plant Athila/Tat elements (within Ty3/Gypsy retrotransposons) independently evolved a dual RNase H domain and an env/env-like gene. Here, we reported the discovery of a novel lineage of retrotransposons, designated Odin retrotransposons, in the genomes of eight sea anemones (order Actinaria) within the Cnidaria phylum. Odin retrotransposons exhibited unique genome features, encoding a dual RNase H domain (like retroviruses) but no env gene (like most Ty3/Gypsy retrotransposons). Phylogenetic analyses based on reverse transcriptase showed that Odin retrotransposons formed a sister group to lokiretroviruses, and lokiretroviruses and Odin retrotransposons together were sister to canonical retroviruses. Moreover, phylogenetic analyses based on RNase H and integrase also supported the hypothesis that Odin retrotransposons were sisters to lokiretroviruses. Lokiretroviruses and canonical retroviruses did not form a monophyletic group, indicating that lokiretroviruses and canonical retroviruses might represent two distinct virus families. Taken together, the discovery of Odin retrotransposons narrowed down the evolutionary gaps between retrotransposons and canonical retroviruses and lokiretroviruses. IMPORTANCE The origin of retroviruses remains largely unclear. In this study, we discovered a novel retrotransposon lineage, Odin retrotransposons, within the genomes of sea anemones (order Actinaria). In contrast to retroviruses and most retrotransposons, Odin retrotransposons encode a dual RNase H domain but no env gene. Phylogenetic analyses showed that Odin retrotransposons were sisters to lokiretroviruses, and lokiretroviruses and Odin retrotransposons were sisters to retroviruses, establishing an evolutionary framework to decipher the origin of retroviruses (canonical retroviruses and lokiretroviruses). Our results provided insights into the diversity and deep evolution of LTR retrotransposons closely related to retroviruses.

Dataset Information

An Amidinohydrolase Provides the Missing Link in the Biosynthesis of Amino Marginolactone Antibiotics.

Publications

An Amidinohydrolase Provides the Missing Link in the Biosynthesis of Amino Marginolactone Antibiotics.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets