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16
4.1 SAT and PT domain:
These domains were detected with the UMA algorithm but early detection was not possible since they showed no homology with any other sequences in the Protein Data Bank (PDB). With the help of UMA, they were expressed discretely and their function was demonstrated in vitro to realize their role. They also showed that SAT is present in many NR PKSs and that they played the major role in determining and selecting the starter unit for biosynthesis.
4.1.1 SAT
Various studies have shown that fungal PKSs typically select acetyl CoA rather than malonyl CoA as a starter unit to initiate biosynthesis of a polyketide, and this has come to be termed as the acetyl „starter unit‟ effect. But recent studies have shown that fungal PKSs are capable of accepting acyl chains or starter units of higher carbon number especially when they are downstream of other PKSs or associated with other fungal systems like NRPSs or FASs. For example, an NR-PS uses a C6 starter unit in the biosynthesis of aflatoxin. This discovery resulted from the analysis of the N-terminal amino domain. The undetermined long amino terminal domain in an NR-PKS was studied through mutation studies
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 22 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 16 4.1 SAT and PT domain: These domains were detected with the UMA algorithm but early detection was not possible since they showed no homology with any other sequences in the Protein Data Bank (PDB). With the help of UMA, they were expressed discretely and their function was demonstrated in vitro to realize their role. They also showed that SAT is present in many NR PKSs and that they played the major role in determining and selecting the starter unit for biosynthesis. 4.1.1 SAT Various studies have shown that fungal PKSs typically select acetyl CoA rather than malonyl CoA as a starter unit to initiate biosynthesis of a polyketide, and this has come to be termed as the acetyl „starter unit‟ effect. But recent studies have shown that fungal PKSs are capable of accepting acyl chains or starter units of higher carbon number especially when they are downstream of other PKSs or associated with other fungal systems like NRPSs or FASs. For example, an NR-PS uses a C6 starter unit in the biosynthesis of aflatoxin. This discovery resulted from the analysis of the N-terminal amino domain. The undetermined long amino terminal domain in an NR-PKS was studied through mutation studies |
