Heterologous Expression of the Biosynthetic Gene Cluster for Verticilactam and Identification of Analogues.

Journal of Natural Products
Toshihiko NogawaShunji Takahashi

Abstract

Verticilactam and the new geometric isomers, verticilactams B and C, were produced by heterologous expression of the biosynthetic gene cluster for verticilactam using the Streptomyces avermitilis SUKA17 strain. Only verticilactam, a compound with a characteristic β-ketoamide unit within a 16-membered polyketide macrolactam conjugated with an octalin skeleton, had been previously reported having been isolated from Streptomyces spiroverticillatus JC-8444. In this report, minor verticilactam derivatives were isolated from the transformed strain, and their structures elucidated by spectral analysis. Verticilactam B was a geometric isomer at Δ17 and Δ19, and verticilactam C was the Δ19 and Δ21 isomer. In addition, the absolute configuration of verticilactam was confirmed by ECD analysis and NMR chemical shifts. The stereochemistry assignments of the hydroxy groups at C-10 and C-12 were supported by the domain organization of the polyketide synthase identified in the verticilactam gene cluster. Verticilactam showed moderate activity against the malaria parasite Plasmodium falciparum 3D7 strain with no significant cytotoxicity or antimicrobial effects.

References

Apr 9, 2005·The Journal of Antibiotics·János Bérdy
Aug 12, 2006·Physical Chemistry Chemical Physics : PCCP·Yihan ShaoMartin Head-Gordon
Apr 19, 2007·Journal of Natural Products·Josefin LarssonAnders Backlund
Aug 28, 2007·Chemistry & Biology·Adrian T Keatinge-Clay
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Mamoru KomatsuHaruo Ikeda
Sep 18, 2010·Organic Letters·Toshihiko NogawaHiroyuki Osada
Mar 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Luisa LauretiBertrand Aigle
Mar 13, 2012·Current Opinion in Chemical Biology·Naoki KatoHiroyuki Osada
May 30, 2013·The Journal of Antibiotics·Toshihiko NogawaHiroyuki Osada
Feb 9, 2016·Journal of Natural Products·David J Newman, Gordon M Cragg
Sep 8, 2016·The Journal of Antibiotics·Toshihiko NogawaHiroyuki Osada
Feb 9, 2017·The Journal of Antibiotics·Shun SaitoMasaya Imoto
Jan 22, 2019·Chemistry : a European Journal·Benjamin R LichmanHajo Kries

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.