Editing Polyketide (section)

=== Polyketide synthase ===
Polyketides are produced by [[polyketide synthase]]s (PKSs). The core biosynthesis involves stepwise condensation of a starter unit (typically [[acetyl-CoA]] or [[propionyl-CoA]]) with an extender unit (either [[malonyl-CoA]] or methylmalonyl-CoA). The condensation reaction is accompanied by the decarboxylation of the extender unit, yielding a beta-keto functional group and releasing a carbon dioxide.<ref name="Voet">{{cite book|title = [[Fundamentals of Biochemistry: Life at the Molecular Level]]| vauthors=Voet D, Voet JG, Pratt CW |authorlink1= Donald Voet|authorlink2= Judith G. Voet|authorlink3= Charlotte W. Pratt|edition= 4th|publisher= [[John Wiley & Sons]]|year= 2013|page= 688|isbn= 9780470547847}}</ref> The first condensation yields an acetoacetyl group, a diketide. Subsequent condensations yield triketides, tetraketide, etc.<ref>{{cite journal | vauthors = Staunton J, Weissman KJ |title=Polyketide biosynthesis: a millennium review |journal=Natural Product Reports |volume=18 |issue=4 |pages=380–416 |date=August 2001 |pmid=11548049 |doi=10.1039/a909079g}}</ref> Other starter units attached to a [[Coenzyme A|coezyme A]] include [[isobutyrate]], [[cyclohexanecarboxylate]], [[malonate]], and [[benzoate]].<ref>{{cite journal |vauthors=Moore BS, Hertweck C |title=Biosynthesis and attachment of novel bacterial polyketide synthase starter units |journal=Natural Product Reports |volume=19 |issue=1 |pages=70–99 |date=February 2002 |pmid=11902441 |doi=10.1039/B003939J}}</ref>

PKSs are multi-domain enzymes or enzyme complex consisting of various domains. The polyketide chains produced by a minimal [[polyketide synthase]] (consisting of a [[acyltransferase]] and [[ketosynthase]] for the stepwise condensation of the starter unit and extender units) are almost invariably modified.<ref>{{cite journal |vauthors=Wang J, Zhang R, Chen X, Sun X, Yan Y, Shen X, Yuan Q |display-authors=3|title=Biosynthesis of aromatic polyketides in microorganisms using type II polyketide synthases |journal=Microbial Cell Factories |volume=19 |issue=1 |pages=110 |date=May 2020 |pmid=32448179 |pmc=7247197 |doi=10.1186/s12934-020-01367-4 |doi-access=free }}</ref> Each polyketide synthases is unique to each polyketide chain because they contain different combinations of domains that reduce the carbonyl group to a hydroxyl (via a [[ketoreductase]]), an olefin (via a [[dehydratase]]), or a methylene (via an [[enoylreductase]]).<ref>{{cite journal |vauthors=Moretto L, Heylen R, Holroyd N, Vance S, Broadhurst RW |display-authors=3|title=Modular type I polyketide synthase acyl carrier protein domains share a common N-terminally extended fold |journal=Scientific Reports |volume=9 |issue=1 |pages=2325 |date=February 2019 |pmid=30787330 |doi=10.1038/s41598-019-38747-9 |pmc=6382882 |bibcode=2019NatSR...9.2325M}}</ref>

Termination of the polyketide scaffold biosynthesis can also vary. It is sometimes accompanied by a [[thioesterase]] that releases the polyketide via hydrating the thioester linkage (as in fatty acid synthesis) creating a linear polyketide scaffold. However, if water is not able to reach the active site, the hydrating reaction will not occur and an intramolecular reaction is more probable creating a macrocyclic polyketide. Another possibility is spontaneous hydrolysis without the aid of a thioesterase.<ref name=":1">{{Cite book| vauthors = Walsh C, Tang Y |url=https://www.worldcat.org/oclc/985609285|title=Natural product biosynthesis |date=2017|publisher=Royal Society of Chemistry |isbn=978-1-78801-131-0|language=English|oclc=985609285}}</ref>