Identification of biosynthetic genes for the β-carboline alkaloid kitasetaline and production of the fluorinated derivatives by heterologous expression

Journal of Industrial Microbiology & Biotechnology
Shohei UedaShigeru Kitani

Abstract

β-Carboline alkaloids exhibit a broad spectrum of pharmacological and biological activities and are widely distributed in nature. Genetic information on the biosynthetic mechanism of β-carboline alkaloids has not been accumulated in bacteria, because there are only a few reports on the microbial β-carboline compounds. We previously isolated kitasetaline, a mercapturic acid derivative of a β-carboline compound, from the genetically modified Kitasatospora setae strain and found a plausible biosynthetic gene cluster for kitasetaline. Here, we identified and characterized three kitasetaline (ksl) biosynthetic genes for the formation of the β-carboline core structure and a gene encoding mycothiol-S-conjugate amidase for the modification of the N-acetylcysteine moiety by using heterologous expression. The proposed model of kitasetaline biosynthesis shows unique enzymatic systems for β-carboline alkaloids. In addition, feeding fluorotryptophan to the heterologous Streptomyces hosts expressing the ksl genes led to the generation of unnatural β-carboline alkaloids exerting novel/potentiated bioactivities.

References

Mar 30, 2004·Biochemical and Biophysical Research Communications·Yongcheng SongRobert Z Qi
May 4, 2004·Chembiochem : a European Journal of Chemical Biology·Peter Jeschke
Feb 9, 2007·FEMS Microbiology Reviews·Mamta Rawat, Yossef Av-Gay
Feb 20, 2007·Current Medicinal Chemistry·Rihui CaoAnlong Xu
Dec 18, 2007·Journal of the American Chemical Society·Justin J MareshSarah E O'Connor
May 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Mamoru KomatsuHaruo Ikeda
Sep 17, 2008·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·László F Szabó
Nov 26, 2008·Natural Product Reports·Vishnu Karthik Jothivasan, Chris J Hamilton
Jul 25, 2009·Applied Microbiology and Biotechnology·Cormac D MurphyJessica Amadio
Dec 29, 2009·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·T HerraizH Guillén
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Mamoru KomatsuHaruo Ikeda
Aug 11, 2011·Angewandte Chemie·Joachim StöckigtHerbert Waldmann
May 9, 2012·Journal of Bioscience and Bioengineering·Aiyada AroonsriTakuya Nihira
Feb 26, 2013·Environmental Toxicology and Pharmacology·Dae-Sung LeeMyung-Suk Lee
Oct 6, 2015·Movement Disorders Clinical Practice·Atbin DjamshidianAndrew J Lees

❮ Previous
Next ❯

Citations

Sep 11, 2020·Free Radical Biology & Medicine·Stephanie BellmaineAline Zimmer

❮ Previous
Next ❯

Datasets Mentioned

BETA
GM2929

Methods Mentioned

BETA
PCR
column chromatography
NMR

Software Mentioned

imageJ

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.