Mechanism and engineering of polyketide chain initiation in fredericamycin biosynthesis.
The ability to incorporate atypical primer units through the use of dedicated initiation polyketide synthase (PKS) modules offers opportunities to expand the molecular diversity of polyketide natural products. Here we identify the initiation PKS module responsible for hexadienyl priming of the antibiotic fredericamycin and investigate its biochemical properties. We also exploit this PKS module for the design and in vivo biosynthesis of unusually primed analogues of a representative polyketide product, thereby emphasizing its utility to the metabolic engineer.
Das
Abhirup
A
Department of Chemistry, Stanford University, Stanford, California 94305, USA.
Szu
Ping-Hui
PH
Fitzgerald
Jay T
JT
Khosla
Chaitan
C
D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D007546:Isoquinolines / Q000378:metabolism; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism*; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods*; D013141:Spiro Compounds / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity
D000900:Anti-Bacterial Agents; D007546:Isoquinolines; D018942:Macrolides; D013141:Spiro Compounds; D048630:Polyketide Synthases; C016660:fredericamycin A