Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• engineering strategies in the light of the newly emerging structural information on megasynthases, and argue that fatty acid synthases (FAS) are and will be valuable objects for further developing this field. Keywords: fatty acid synthases; megasynthases; metabolic enzyme engineering; polyketide synthases

• a single module repeatedly condensing precursor units until the specific length/size is attained (iterative systems) [4]. In either case, the enzymatic functions of each module deterministically encode the chemical nature of the final product [5]. Fatty acid synthases (FAS) are a type of PKS

• biosynthesis as performed by fatty acid synthases (FAS). Synthesis by PKS is essentially similar, except a variation in the degree of β-carbon modification, and the variation in loading and exit transferases. Modular PKS perform one cycle per module before translocating the substrate to the next module

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

• 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

• ) animal fatty acid synthases and that on bacterial modular polyketide synthases, and it also hints at what could be a major mechanism for the evolution of these processive systems. Nevertheless, the highly repetitive nature of the genes encoding modular PKS makes it easy to misassemble sequence data, and

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

• synthase (NorS) (Scheme 16) [83][85]. NorS is a complex of a NR-PKS PksA and a pair of yeast-like fatty acid synthases HexA/HexB, which provide an unusual hexanoyl-CoA starter unit [86]. Norsolorinic acid (100) undergoes three oxidative rearrangements towards aflatoxin B1 (94): The first rearrangement sets

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• modular fashion [15]. In contrast to fatty acid synthases (FAS), PKSs do not necessarily process the initially formed 3-keto functions through a complete reductive cycle, which leads to structurally diverse products as shown in Figure 1 for lovastatin (1), an inhibitor of 3-hydroxy-3-methylglutaryl CoA

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• by fatty acid synthases to the final iso-fatty acids (even numbered for isobutyryl-CoA; odd-numbered for isovaleryl-CoA) through extension with malonyl-CoA [21][22]. Long-chain iso-fatty acids are important analytical reference compounds owing to the presence of these materials in tobacco [23], wool

Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

• Stephan Klopries,
• Uschi Sundermann and
• Frank Schulz

Beilstein J. Org. Chem. 2013, 9, 664–674, doi:10.3762/bjoc.9.75

• widespread application in current medicine and agriculture. Polyketide synthases (PKS), giant multienzyme complexes, play a pivotal role in their biosynthesis. PKS generate molecular complexity and diversity through a number of stepwise condensations in analogy to fatty acid synthases but with optional and