In: Chemistry
Identify all the biosynthetic subunit in Rapamycin
The biosynthesis of the rapamycin core is accomplished by a type
I polyketide synthase (PKS) in conjunction with a nonribosomal
peptide synthetase (NRPS). The domains responsible for the
biosynthesis of the linear polyketide of rapamycin are organized
into three multienzymes, RapA, RapB, and RapC, which contain a
total of 14 modules. These module pic is also attached at the
end.The three multienzymes are organized such that the first four
modules of polyketide chain elongation are in RapA, the following
six modules for continued elongation are in RapB, and the final
four modules to complete the biosynthesis of the linear polyketide
are in RapC. Then, the linear polyketide is modified by the NRPS,
RapP, which attaches L-pipecolate to the terminal end of the
polyketide, and then cyclizes the molecule, yielding the unbound
product, prerapamycin. The core macrocycle, prerapamycin (figure
2), is then modified (figure 3) by an additional five enzymes,
which lead to the final product, rapamycin. First, the core
macrocycle is modified by RapI, SAM-dependent O-methyltransferase
(MTase), which O-methylates at C39. Next, a carbonyl is installed
at C9 by RapJ, a cytochrome P-450monooxygenases (P-450). Then,
RapM, another MTase, O-methylates at C16. Finally, RapN, another
P-450, installs a hydroxyl at C27 immediately followed by
O-methylation by Rap Q, a distinct MTase, at C27 to yield
rapamycin.