Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase

• Hui Hong,
• Yuhui Sun,
• Yongjun Zhou,
• Emily Stephens,
• Markiyan Samborskyy and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2016, 12, 2164–2172, doi:10.3762/bjoc.12.206

• gene cluster for biosynthesis of the polyketide β-lactone ebelactone in Streptomyces aburaviensis has shown that, contrary to a recently-published proposal, the ebelactone polyketide synthase faithfully follows the colinear modular paradigm. Keywords: colinearity; ebelactone; enzyme catalysis

• Stigmatella aurantiaca [20], further examples have been uncovered in the PKSs for aureothin [21][22], borrelidin [23][24], lankacidin [25][26], neoaureothin [27], etnangien [28], crocacin [29], ebelactone [30] and thiolactomycin [31][32]. Given the close mechanistic analogy between fatty acid synthases and an

• the third is the PKS for the β-lactone ebelactone, a potent esterase inhibitor from Streptomyces aburaviensis 2a,b (Figure 1) [30]. These examples are particularly interesting as potential model systems because the chemical outcome of the two successive extensions catalysed by the iterative module is

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• -2-one. Concomitant attack of the intermediately formed hydroxylate on the thioester closes the β-lactone and releases salinosporamide A (199) from the assembly line. Ebelactone A. Ebelactone A (201) is an esterase inhibitor of PKS type I origin that is produced by Streptomyces aburaviensis ATCC 31

• of the β-hydroxy group on the thioester of 200, resulting in the off-loaded ebelactone A (201) (Scheme 28) [163]. The β-lactone moiety of the human pancreatic lipase inhibitor lipstatin is also formed in a similar fashion. 2 Nitrogen-containing heterocycles Nitrogen-containing heterocycles are