Starter unit specificity directs genome mining of polyketide synthase pathways in fungi.

Bioorganic Chemistry
Jason M CrawfordCraig A Townsend

Abstract

Search of the protein database with the aflatoxin pathway polyketide synthase (PKS) revealed putative PKSs in the pathogenic fungi Coccidioides immitis and Coccidioides posadasii that could require partnerships with a pair of fatty acid synthase (FAS) subunits for the biosynthesis of fatty acid-polyketide hybrid metabolites. A starter unit:acyl-carrier protein transacylase (SAT) domain was discovered in the nonreducing PKS. This domain is thought to accept the fatty acid product from the FAS to initiate polyketide synthesis. We expressed the C. immitis SAT domain in Escherichia coli and showed that this domain, unlike that from the aflatoxin pathway PKS, transferred octanoyl-CoA four times faster than hexanoyl-CoA. The SAT domain also formed a covalent octanoyl intermediate and transferred this group to a free-standing ACP domain. Our results suggest that C. immitis/posadasii, both human fungal pathogens, contain a FAS/PKS cluster with functional similarity to the aflatoxin cluster found in Aspergillus species. Dissection of the PKS and determination of in vitro SAT domain specificity provides a tool to uncover the growing number of similar sequenced pathways in fungi, and to guide elucidation of the fatty acid-polyketide hybri...Continue Reading

References

Dec 24, 2005·Nature·Masayuki MachidaHisashi Kikuchi
Nov 1, 2006·Fungal Genetics and Biology : FG & B·Joshua D NosanchukGarry T Cole

❮ Previous
Next ❯

Citations

Apr 12, 2008·Science·Jason M CrawfordCraig A Townsend
Apr 3, 2010·Applied Microbiology and Biotechnology·Yi-Ming ChiangClay C C Wang
Nov 17, 2010·Nature Reviews. Microbiology·Jason M Crawford, Craig A Townsend
Apr 19, 2012·Journal of the American Chemical Society·Manmeet AhujaClay C C Wang
Oct 20, 2012·Fungal Genetics and Biology : FG & B·Gerald LacknerDirk Hoffmeister
Oct 8, 2015·Nucleic Acids Research·Michael A SkinniderNathan A Magarvey
Jul 15, 2015·Journal of the American Chemical Society·Jaclyn M WinterYi Tang
Apr 14, 2009·Methods in Enzymology·Russell J Cox, Thomas J Simpson
Feb 28, 2017·Journal of the American Chemical Society·Eric P TrautmanJason M Crawford
Jun 13, 2009·Journal of Industrial Microbiology & Biotechnology·K M FischR H Cichewicz
Jan 1, 2012·Metabolites·Marie L KlejnstrupJakob B Nielsen
Apr 12, 2012·Applied and Environmental Microbiology·Lena StudtBettina Tudzynski
Apr 12, 2012·Applied and Environmental Microbiology·Fang Yun LimNancy P Keller
Mar 14, 2008·Chembiochem : a European Journal of Chemical Biology·Jason M CrawfordCraig A Townsend
Nov 26, 2009·Natural Product Reports·Imke Schmitt, F Keith Barker
Feb 9, 2010·Chembiochem : a European Journal of Chemical Biology·Madan K KharelJürgen Rohr

❮ 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.