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19
Studies of the SAT domain in the norsolorinic acids synthase (NSAS) family of NR-PKSs suggested that the SAT domain could accept hexanoate or acetyl as the starter unit, and it relied on steric hindrance to achieve that. The residue situated upstream of the active site His in the catalytic dyad of SAT domain contains a conserved Ala for the hexanoyl acceptors while it mutates to a bulky Phe or Tyr for the acetyl acceptors.[2] This shows how the SAT domain operates to selectively accept the starter unit. Another reason stated for the preferential acceptance of acetyl in vivo is the ready availability of it during metabolism since it is a precursor in the TCA cycle. It has been shown that SAT domains can accept carbon chains of varied length and this selectivity in choosing the starter unit forms a basis for the structural variations that we observe in polyketide products.
The lack of use of acetyl as a starter unit has also observed before in Colletotrichum lagenarium PKS1, which uses malonyl-CoA as the starter unit and also in Pks4 from Gibberella fujikuroi. [12]
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 25 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 19 Studies of the SAT domain in the norsolorinic acids synthase (NSAS) family of NR-PKSs suggested that the SAT domain could accept hexanoate or acetyl as the starter unit, and it relied on steric hindrance to achieve that. The residue situated upstream of the active site His in the catalytic dyad of SAT domain contains a conserved Ala for the hexanoyl acceptors while it mutates to a bulky Phe or Tyr for the acetyl acceptors.[2] This shows how the SAT domain operates to selectively accept the starter unit. Another reason stated for the preferential acceptance of acetyl in vivo is the ready availability of it during metabolism since it is a precursor in the TCA cycle. It has been shown that SAT domains can accept carbon chains of varied length and this selectivity in choosing the starter unit forms a basis for the structural variations that we observe in polyketide products. The lack of use of acetyl as a starter unit has also observed before in Colletotrichum lagenarium PKS1, which uses malonyl-CoA as the starter unit and also in Pks4 from Gibberella fujikuroi. [12] |
