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24
4.1.2 PT structure and cyclization selectivity:
Townsend and colleagues next dissected PksA into seven additional units and then recombined them in a combinatorial manner in vitro. By analyzing the resulting products, they were able to confirm the presumed activities of the standard domains (KS, AT, ACP), as well as to demonstrate directly the novel function of the PT. [13]
The structural variability of aromatic products of fungal nonreducing, multidomain iterative polyketide synthases (NR-PKS) of group IPKSs (iterative polyketide synthases) results from regiospecific cyclizations of reactive poly-β- keto intermediates. [14-15] A mutational study conducted on a dissected product template (PT) domain from PksA, a NR-PKS that is responsible for synthesis of aflatoxin B1, showed that it was responsible for controlling aldol cyclization and aromatization of polyketide intermediates.[14, 16]
The PT domain is in the form also seen in some bacterial dehydrase-isomerases and mammalian hydratases. The domain proved to have a distinct „double hot dog‟ fold and also displayed binding to both palmitates and bicyclic products. This showed that the PT domain can bind to linear and cyclic compounds. Interestingly, in the PT domains of
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 30 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 24 4.1.2 PT structure and cyclization selectivity: Townsend and colleagues next dissected PksA into seven additional units and then recombined them in a combinatorial manner in vitro. By analyzing the resulting products, they were able to confirm the presumed activities of the standard domains (KS, AT, ACP), as well as to demonstrate directly the novel function of the PT. [13] The structural variability of aromatic products of fungal nonreducing, multidomain iterative polyketide synthases (NR-PKS) of group IPKSs (iterative polyketide synthases) results from regiospecific cyclizations of reactive poly-β- keto intermediates. [14-15] A mutational study conducted on a dissected product template (PT) domain from PksA, a NR-PKS that is responsible for synthesis of aflatoxin B1, showed that it was responsible for controlling aldol cyclization and aromatization of polyketide intermediates.[14, 16] The PT domain is in the form also seen in some bacterial dehydrase-isomerases and mammalian hydratases. The domain proved to have a distinct „double hot dog‟ fold and also displayed binding to both palmitates and bicyclic products. This showed that the PT domain can bind to linear and cyclic compounds. Interestingly, in the PT domains of |
