Abstract
Cryptosporidium parvum is a globally important zoonotic parasite capable of causing severe to deadly diarrhea in humans and animals. Its small genome (~9.1 Mb) encodes not only a highly streamlined metabolism, but also a 25-kb, 3-module fatty acid synthase (CpFAS1) and a 40-kb, 7-module polyketide synthase (CpPKS1). The two megasynthases contain a C-terminal reductase domain to release the final products with predicted chain lengths of ≥C22 for CpFAS1 or C28 to C38 for CpPKS1.The parasite genome also encodes a discrete thioesterase ortholog, suggesting its role to be an alternative tool in releasing the final products from CpFAS1 and/or CpPKS1, or as an editor to remove non-reactive residues or aberrant intermediates, or to control starter units as seen in other parasites. In this study, we have confirmed that this C. parvum thioesterase is a type II thioesterase (thus named as CpTEII). CpTEII contains motifs and a catalytic triad characteristic to the type II thioesterase family. CpTEII is expressed during the entire parasite life cycle stages with the highest levels of expression in the later developmental stages. CpTEII showed the highest hydrolytic activity toward C10:0 decanoyl-CoA, so we speculated that CpTEII may mainly act as an editor to remove non-reactive residues and/or aberrant medium acyl chain from CpFAS1 and/or CpPKS1. However, we cannot rule out the possibility that CpTEII may also participate in the release of final products from CpFAS1 because of its moderate activity on C20:0, C:22:0 and C24:0 acyl-CoA thioesters (i.e., ~20–30% activity vs. decanoyl-CoA).
Highlights
Cryptosporidium parvum is a protozoan parasite, which belongs to the Phylum Apicomplexa and is a causative agent of cryptosporidiosis in humans and various animals (Tzipori and Widmer, 2008; Ryan et al, 2014)
Cryptosporidiosis is associated with high morbidity and mortality rate worldwide, and is one of top four pathogens causing moderate to severe diarrhea in infants under the age of two in developing countries (Kotloff et al, 2013; Checkley et al, 2015)
We report the characterization of the molecular and biochemical features of a TEII from C. parvum (CpTEII) for the first time in a protozoan
Summary
Cryptosporidium parvum is a protozoan parasite, which belongs to the Phylum Apicomplexa and is a causative agent of cryptosporidiosis in humans and various animals (Tzipori and Widmer, 2008; Ryan et al, 2014). This parasite has two megasynthases: a 921 kDa type I fatty acid synthase (CpFAS1) and a 1,516 kDa type I polyketide synthase (CpPKS1) (Zhu et al, 2002, 2004, 2010). These two megasynthases are unable to synthesize fatty acyl or polyketide chains de novo, but likely responsible for synthesizing very long-chain fatty acyl or polyketide alcohols using longchain fatty acids as the starter units, because both CpFAS1 and CpPKS1 have been confirmed to have substrate preference toward long-chain fatty acids. Terminating domain of CpFAS1 prefers to hydrolyze very long-chain fatty acids (Fritzler and Zhu, 2007; Zhu et al, 2010)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
