New Insights on Cyclization Specificity of Fungal Type III Polyketide Synthase, PKSIIINc in Neurospora crassa

Indian Journal of Microbiology
Amreesh ParvezPriti Saxena

Abstract

Type III polyketide synthases (PKSs) biosynthesize varied classes of metabolites with diverse bio-functionalities. Inherent promiscuous substrate specificity, multiple elongations of reaction intermediates and several modes of ring-closure, confer the proteins with the ability to generate unique scaffolds from limited substrate pools. Structural studies have identified crucial amino acid residues that dictate type III PKS functioning, though cyclization specific residues need further investigation. PKSIIINc, a functionally and structurally characterized type III PKS from the fungus, Neurospora crassa, is known to biosynthesize alkyl-resorcinol, alkyl-triketide- and alkyl-tetraketide-α-pyrone products. In this study, we attempted to identify residue positions governing cyclization specificity in PKSIIINc through comparative structural analysis. Structural comparisons with other type III PKSs revealed a motif with conserved hydroxyl/thiol groups that could dictate PKSIIINc catalysis. Site-directed mutagenesis of Cys120 and Ser186 to Ser and Cys, respectively, altered product profiles of mutant proteins. While both C120S and S186C proteins retained wild-type PKSIIINc product activity, S186C favoured lactonization and yielded highe...Continue Reading

References

Jul 30, 1999·Nature Structural Biology·J L FerrerJ P Noel
Nov 28, 2001·The Journal of Biological Chemistry·Nobutaka FunaSueharu Horinouchi
Aug 3, 2004·Nature Structural & Molecular Biology·Rajan SankaranarayananRaju Rukmini
Apr 7, 2006·Proceedings of the National Academy of Sciences of the United States of America·Nobutaka FunaSueharu Horinouchi
May 9, 2008·Journal of Structural Biology·Aneesh GoyalRajan Sankaranarayanan
Sep 6, 2012·International Journal of Molecular Sciences·Raja Noor Zaliha Raja Abdul RahmanMahiran Basri
Mar 15, 2014·Critical Reviews in Biochemistry and Molecular Biology·Luis E N Quadri
Sep 4, 2014·Natural Product Reports·Makoto HashimotoIsao Fujii
Feb 28, 2015·Critical Reviews in Biotechnology·Krishna Kant Sharma
Nov 10, 2015·Applied Microbiology and Biotechnology·Haotong Chen, Liangcheng Du
Jan 18, 2016·Fungal Genetics and Biology : FG & B·Theo A J van der Lee, Marnix H Medema
Feb 7, 2016·Fungal Genetics and Biology : FG & B·Carly BondLi Li
Jun 25, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yan Ping LimWen Shan Yew
Nov 20, 2016·Chembiochem : a European Journal of Chemical Biology·Yugo ShimizuSusumu Goto
Mar 17, 2017·F1000Research·Zhuan ZhangGong-Li Tang
May 4, 2017·Chembiochem : a European Journal of Chemical Biology·Changsheng WuGilles P van Wezel
Aug 7, 2017·Nature Reviews. Microbiology·Mareike Möller, Eva H Stukenbrock
Aug 22, 2017·IMA Fungus·Janneke AylwardMichael J Wingfield
Feb 10, 2018·Sheng wu gong cheng xue bao = Chinese journal of biotechnology·Xiwei ChenChanghua Hu
Feb 28, 2018·Journal of Natural Products·Robert L BertrandJohn L Sorensen

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray

Software Mentioned

Biovia Discovery Studio
Discovery Studio
CHARMM

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.