Question

(b) One method of obtaining novel variants of erythromycin is to introduce mutations into the PKS genes and thereby remove the enzyme activity associated with a given domain. By writing down the transformations catalysed by each domain of DEBS1 and DEBS2, select which of the following four novel erythromycin derivatives (8-11) would be obtained if the first enoylreductase domain (ER) in DEBS2 were rendered inactive by mutation. Curly-arrow mechanisms for each step are not required. (4 points) Hoʻ =o HO EO HO =0 - HO HOL HO

Answer 1

Polyketide synthases (PKS) are multifunctiona catalytic machine it occurs the biosynthess of a structurally diverse range of Natural Products. The 6-deoxyerythronolide B synther (DEBS) is an Le Re Ye homodimer with a molecular mass exceeding 2. MD. which is comprised minimally of en Ketosynthase an acyltransferase (AT), and anded -cossier Protein (ACP) domain. Thus, the truncated derivatives of DEBS shown in the propional Primer ès KS1 domain shown. The first two modules are shownina distinct color, where as the clomain of module 3 care colored for ease of comparison with the cryo-EM derived molel of pikalt and SAXS-derived model of DE BS. DEBSI and DEBS 2 interface between modules 2 and 3 illustrated for the truncated DEBS as well as for the interface between DEBS2 and DGBS3. The Rs and AT domains are separated by a linking domain with a ferredosein like protein fold. The grey tabs refer to Peptide docking domains chains located in distinct Polybe bride chains sech as modules 2 and 3.