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5.1 RECENT ADVANCES IN HIGHLY REDUCED POLYKETIDE SYNTASES:
Whole feeding experiments of doubly (13C, 2H) labeled acetate to cultures of A. terreus in the study of LovB (HR-PKS that synthesizes lovastatin) were performed to examine the activity of typical HR polyketide sythases and the importance of cofactors as a part of their activity. It was seen that LovB can use malonyl CoA for priming as well as chain elongation. It loads malonyl group and carry out de-carboxylation to form the starter acetate unit. [11]. This section will discuss roles of domains in HR-PKSs discovered in the past few years.
5.1.1 ROLE OF NADPH IN FUCTIONING OF KR DOMAIN:
While LovB elongates the chain by condensation, it was seen that in the absence of NADPH no ketoreduction took place and the dominant product that was off-loaded was lactone 3 after enolization and cyclization. On addition of NADPH, the function of the KR domain is enabled. [11]
With KR enabled, LovB makes penta-, hexa- and heptaketide pyrones 4-6 as well as ketones. All these structures were confirmed through chemical
Object Description
| Title | Fungal polyketides -- Review of recent findings |
| Author | Jain, Sofina M. |
| Author email | sofinaja@usc.edu; sofinajain27@gmail.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Pharmacy / Pharmaceutical Sciences |
| School | School of Pharmacy |
| Date defended/completed | 2011-05-04 |
| Date submitted | 2011 |
| Restricted until | Unrestricted |
| Date published | 2011-05-05 |
| Advisor (committee chair) | Wang, Clay C. C. |
| Advisor (committee member) |
Okamoto, Curtis Toshio Shen, Wei-Chiang |
| Abstract | Fungal polyketides are a group of bioactive compounds which have found use in humans as anti-cholesterol, anti-cancer and antibiotic agents. These are synthesized by a group of enzymes called the polyketide synthases (PKSs) which are found in fungi as well as bacteria. PKSs are classified as type I, II and III. All fungal PKSs are type I iterative polyketide synthases which means they use a set of catalytic functions by a group of active domains in repetitive cycles to give the end product. Type I enzymes contain multidomains that catalyze a set of reactions.; The minimal PKS contains the domains ketosynthase (KS), acyltransferase (AT) and acyl carrier protein (ACP). The three types of PKSs are non-reduced polyketide synthases (NR-PKSs), highly-reduced polyketide synthases (HR-PKSs) and partially-reduced polyketide synthases (PR-PKSs). This classification is another form separate from type I, II and III. This paper discusses the recent research into further details of the SAT, PT and TE domain of the NR-PKSs and also recent advances in the HR-PKSs. This paper will also discuss the role of NADPH, SAM and CON domain in the HR-PKSs. We will also discuss the two off-loading mechanism of HR-PKSs that were seen in recent papers. While little research is done on PR-PKSs, NR-PKS and HR-PKS are extensively being worked on.Recent findings have brought us a step closer to the domains of the PKSs and promise us a better clearer understanding of this complex multidomain entity. |
| Keyword | fungal polyketides; HR-PKS; NR-PKS; PT domain; SAT domain; TE domain |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m3914 |
| Contributing entity | University of Southern California |
| Rights | Jain, Sofina M. |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | cisadmin@lib.usc.edu |
| Filename | etd-jain-4552 |
| Archival file | uscthesesreloadpub_Volume40/etd-jain-4552.pdf |
Description
| Title | Page 47 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 41 5.1 RECENT ADVANCES IN HIGHLY REDUCED POLYKETIDE SYNTASES: Whole feeding experiments of doubly (13C, 2H) labeled acetate to cultures of A. terreus in the study of LovB (HR-PKS that synthesizes lovastatin) were performed to examine the activity of typical HR polyketide sythases and the importance of cofactors as a part of their activity. It was seen that LovB can use malonyl CoA for priming as well as chain elongation. It loads malonyl group and carry out de-carboxylation to form the starter acetate unit. [11]. This section will discuss roles of domains in HR-PKSs discovered in the past few years. 5.1.1 ROLE OF NADPH IN FUCTIONING OF KR DOMAIN: While LovB elongates the chain by condensation, it was seen that in the absence of NADPH no ketoreduction took place and the dominant product that was off-loaded was lactone 3 after enolization and cyclization. On addition of NADPH, the function of the KR domain is enabled. [11] With KR enabled, LovB makes penta-, hexa- and heptaketide pyrones 4-6 as well as ketones. All these structures were confirmed through chemical |
