An Alternative Isovaleryl CoA Biosynthetic Pathway Involving a Previously Unknown 3‐Methylglutaconyl CoA Decarboxylase

Li, Yanyan; Luxenburger, Eva; Müller, Rolf

doi:10.1002/anie.201207984

Cited by 32 publications

(89 citation statements)

References 28 publications

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“…The E3 subunit of BCKAD was not present on the microarray and thus undetermined. M. xanthus has an additional, novel pathway for making isovaleryl CoA [16]–[18]. Three genes identified in this pathway are up-regulated during development (MXAN4264, 2.9 fold; MXAN4265, 2.0-fold; MXAN4266, 3.8-fold).…”

Section: Resultsmentioning

confidence: 99%

Fatty Acids from Membrane Lipids Become Incorporated into Lipid Bodies during Myxococcus xanthus Differentiation

et al. 2014

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Myxococcus xanthus responds to amino acid limitation by producing fruiting bodies containing dormant spores. During development, cells produce triacylglycerides in lipid bodies that become consumed during spore maturation. As the cells are starved to induce development, the production of triglycerides represents a counterintuitive metabolic switch. In this paper, lipid bodies were quantified in wild-type strain DK1622 and 33 developmental mutants at the cellular level by measuring the cross sectional area of the cell stained with the lipophilic dye Nile red. We provide five lines of evidence that triacylglycerides are derived from membrane phospholipids as cells shorten in length and then differentiate into myxospores. First, in wild type cells, lipid bodies appear early in development and their size increases concurrent with an 87% decline in membrane surface area. Second, developmental mutants blocked at different stages of shortening and differentiation accumulated lipid bodies proportionate with their cell length with a Pearson's correlation coefficient of 0.76. Third, peripheral rods, developing cells that do not produce lipid bodies, fail to shorten. Fourth, genes for fatty acid synthesis are down-regulated while genes for fatty acid degradation are up regulated. Finally, direct movement of fatty acids from membrane lipids in growing cells to lipid bodies in developing cells was observed by pulse labeling cells with palmitate. Recycling of lipids released by Programmed Cell Death appears not to be necessary for lipid body production as a fadL mutant was defective in fatty acid uptake but proficient in lipid body production. The lipid body regulon involves many developmental genes that are not specifically involved in fatty acid synthesis or degradation. MazF RNA interferase and its target, enhancer-binding protein Nla6, appear to negatively regulate cell shortening and TAG accumulation whereas most cell-cell signals activate these processes.

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Section: Resultsmentioning

confidence: 99%

Fatty Acids from Membrane Lipids Become Incorporated into Lipid Bodies during Myxococcus xanthus Differentiation

et al. 2014

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“…The mutation in the bkd locus prevents the formation of isovaleryl-CoA as a precursor for the biosynthesis of iso-fatty acids (9). Even though M. xanthus exhibits an alternative pathway via 3-hydroxy-3-methylglutaryl-CoA (22,32,33), which is upregulated during development, the total amount of iso-15:0 fatty acids is strongly decreased. In addition, ceramides with iso-17:0 fatty acids were less abundant in the esg mutant, as one would expect from the reduction in the level of starting units for the biosynthesis of iso-fatty acids in an esg mutant.…”

Section: Discussionmentioning

confidence: 99%

“…The most abundant fatty acid in M. xanthus, iso-15:0, is synthesized using isovaleryl coenzyme A (CoA) derived from leucine as a starter unit or an alternative biosynthesis pathway (9,9,16,(21)(22)(23). In order to differentiate between fatty acids which are recycled from existing spore material and those synthesized de novo, cells were germinated in medium with equal amounts of leucine and D 10 -leucine.…”

Section: Analysis Of Lipid Samples From Developing M Xanthus Dk1622 mentioning

confidence: 99%

Neutral and Phospholipids of the Myxococcus xanthus Lipodome during Fruiting Body Formation and Germination

Ahrendt

Wolff

Bode

2015

Appl Environ Microbiol

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“…13,14 Therefore, deletion of CHC biosynthesis genes might give these acids more chance to be involved in the biosynthetic pathway of trienomycin A.…”

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confidence: 99%

New ansamycin analogues from the mutant strain of Streptomyces seoulensis

Song

Zhang

et al. 2015

J Antibiot

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Ansamycin antibiotics, derived from 3-amino-5-hydroxybenzoic acid (AHBA), are a group of microbial metabolites that exhibit an extensive range of biological activities such as antitumor, antiviral and antibacterial. [1][2][3][4] The C17-benzene ansamycins (C17BAs), distinguished by their 21-membered macrolactam formed through an amide linkage to the AHBA moiety, have a unique feature with a carboxylic acid moiety attached via an L-alanine residue to the polyketide backbone. [5][6][7][8][9] It is worth noting that the bioactive diversity highly depends on the structure of the acyl chain attached at C-11 and the aromatic ring of C17BAs. 10,11 During our screening for new bioactive C17BA analogs, four known C17BAs, trienomycin A (1), benzoxazomycin (2), mycotrienin II (3) and mycotrienin I (4), were isolated from the fermentation broth of Streptomyces seoulensis IFB-A01 (derived from Penaeus orientalis Kishi-nouye gut). 12 The conversion from 1 to 2 through the intermediates of 3 and 4 has been clarified step by step, together with the discovery of the gene cluster for biosynthesis of 1 in our previous study, 12 which sets up the stage for the further mutasynthesis.The mutant strain S. seoulensis IFB-A01-C, whose genes related to the biosynthesis of the carboxylic side chain (cyclohexanecarboxylic acid, CHC) have been deleted, lost the ability to produce compounds 1-4 completely. 12 However, in the mutant strain three new analogs (1a-1c) were detected as the major HPLC peaks. These compounds had not been isolated previously from the wild-type strain, presumably because of the relatively low yield or overlap by other major peaks. To see whether the wild-type strain can also produce these two products, an LC-MS experiment was conducted to analyze the crude extracts from wild-type and mutant strains. The result unambiguously showed that the wild-type strain indeed can produce 1a-1c with the production yields about 10-20 times lower than those in mutant strain (Supplementary Figure S1). Encouraged by these results, scaleup fermentation of the mutated strain was performed. Isolation, structural elucidation and bioactivity assay of these C17BAs analogs are described in this paper.The culture method and fermentation of the mutant strain of S. seoulensis IFB-A01 were performed according to the earlier report. 12 After 7-day scale-up fermentation, the fermentation (20 l) was extracted three times with ethyl acetate, and evaporation of the solvent under reduced pressure provided a residue for subsequent investigation. Subsequent purification of the column chromatography (CC) fractions that contained the target compounds was accomplished by Sephadex LH-20 and semipreparative HPLC. In particular, purification of the fourth CC fraction derived from the mutant strain culture by gel filtration over Sephadex LH-20 in MeOH and by semipreparative HPLC (50% acetonitrile/H 2 O, 2 ml min − 1 ) to afford pure compounds.In the beginning, compounds 1a-1c were obtained from the extracted fraction. From the NMR analysis, it was found that th...

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An Alternative Isovaleryl CoA Biosynthetic Pathway Involving a Previously Unknown 3‐Methylglutaconyl CoA Decarboxylase

Cited by 32 publications

References 28 publications

Fatty Acids from Membrane Lipids Become Incorporated into Lipid Bodies during Myxococcus xanthus Differentiation

Fatty Acids from Membrane Lipids Become Incorporated into Lipid Bodies during Myxococcus xanthus Differentiation

Neutral and Phospholipids of the Myxococcus xanthus Lipodome during Fruiting Body Formation and Germination

New ansamycin analogues from the mutant strain of Streptomyces seoulensis

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