Editing Amphotericin B (section)

== Biosynthesis ==
The natural route to synthesis includes [[polyketide synthase]] components.<ref>{{cite journal | vauthors = Khan N, Rawlings B, Caffrey P | title = A labile point in mutant amphotericin polyketide synthases | journal = Biotechnology Letters | volume = 33 | issue = 6 | pages = 1121–1126 | date = June 2011 | pmid = 21267757 | doi = 10.1007/s10529-011-0538-3 | s2cid = 10209476 | url = https://hal.science/hal-00663072 }}</ref> The carbon chains of amphotericin B are assembled from sixteen 'C2' acetate and three 'C3'propionate units by polyketide syntheses (PKSs).<ref name = "McNamara_1998">{{cite journal | vauthors = McNamara C, Crawforth J, Hickman B, Norwood T, Rawlings B |date= January 1998 |title=Biosynthesis of amphotericin B|journal=Journal of the Chemical Society, Perkin Transactions 1|pages=83–88|doi=10.1039/A704545J|issue=1|url=https://lra.le.ac.uk/bitstream/2381/33805/1/U087475.pdf|hdl=2381/33805 |hdl-access=free |access-date=2018-05-16 |archive-date=2017-09-21 |archive-url= https://web.archive.org/web/20170921234009/https://lra.le.ac.uk/bitstream/2381/33805/1/U087475.pdf|type= thesis |url-status=dead }}<!--|access-date=2015-05-24 --></ref> Polyketide biosynthesis begins with the decarboxylative condensation of a dicarboxylic acid extender unit with a starter acyl unit to form a β-ketoacyl intermediate. A series of Claisen reactions constructs the growing chain. The extender units are loaded onto the current ACP domain by acetyl transferase (AT) within each module. The ACP-bound elongation group reacts in a Claisen condensation with the KS-bound polyketide chain. Ketoreductase (KR), dehydratase (DH), and enoyl reductase (ER) enzymes may also be present to form alcohol, double bonds, or single bonds.<ref name="Caffrey2001">{{cite journal | vauthors = Caffrey P, Lynch S, Flood E, Finnan S, Oliynyk M | title = Amphotericin biosynthesis in Streptomyces nodosus: deductions from analysis of polyketide synthase and late genes | journal = Chemistry & Biology | volume = 8 | issue = 7 | pages = 713–723 | date = July 2001 | pmid = 11451671 | doi = 10.1016/S1074-5521(01)00046-1 | doi-access = free }}</ref> After cyclisation, the macrolactone core undergoes further modification by hydroxylation, methylation and glycosylation. The order of these three post-cyclization processes is unknown.<ref name="Caffrey2001"/>