Production and utilization of butyryl-CoA by fatty acid synthetase from mammalian tissues

Abdinejad, Ali; Fisher, Alice; Kumar, Soma

doi:10.1016/0003-9861(81)90132-6

Cited by 25 publications

(10 citation statements)

References 27 publications

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“…However, the specificity of the thioester hydrolase released from goat mammary synthetase complex does not agree with the results obtained with the hydrolase component from cow mammary-gland synthetase (Abinejad et al, 1981). At 5p#M-butyryl-CoA the thioester hydrolase released from goat synthetase barely shows hydrolytic activity towards this substrate.…”

Section: Discussioncontrasting

confidence: 58%

“…When measured at 22.5#Mand 45.0,uM-butyryl-CoA the hydrolytic activity was less than 3% and 4% respectively of that towards palmitoyl-CoA at 5,uM (results not shown). The hydrolase component from cow enzyme hydrolysed buturyl-CoA at a rate of 27% of that with palmitoyl-CoA (Abinejad et al, 1981). We find this surprising, since both cow and goat mammary gland synthesize butyric acid in vivo.…”

Section: Discussionmentioning

confidence: 64%

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Medium-chain fatty acid synthesis by goat mammary-gland fatty acid synthetase. The effect of limited proteolysis

Grunnet¹,

Knudsen²

1983

Biochemical Journal

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Fatty acid synthetase from goat mammary gland was subjected to limited proteolysis by trypsin and elastase. Both proteolytic enzymes selectively cleaved the chain-terminating thioester hydrolase component from the enzyme complex, leaving all other partial activities intact in the core peptides. Trypsin, but not elastase, caused extensive degradation of the released thioester hydrolase. The released thioester hydrolase could be purified to homogeneity by gel filtration. The molecular weight was estimated as 29 000 and the enzyme showed only significant hydrolytic activity toward long-chain acyl-CoA esters. The core peptides retained the ability to synthesize medium-chain acyl-CoA esters in the presence of 2,6-di-O-methyl-alpha-cyclodextrin. The results conclusively show that the terminating thioester hydrolase of goat mammary-gland fatty acid synthetase is not involved in termination of medium-chain-length fatty acid synthesis by this enzyme.

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Section: Discussioncontrasting

confidence: 58%

Section: Discussionmentioning

confidence: 64%

Medium-chain fatty acid synthesis by goat mammary-gland fatty acid synthetase. The effect of limited proteolysis

Grunnet¹,

Knudsen²

1983

Biochemical Journal

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“…We determined a specific malonyl consumption rate of 282 ±16 nmol min -1 mg protein -1 which was comparable to the previously reported values for recombinantly produced human FAS. 17,24 In comparison to this, significantly higher activity (3-5 fold) have been reported for animal FASs purified from native tissues and rat FAS, 25,26 expressed in insect cells. This compromised activity may indicate the lack of post-translational modifications, which cannot be provided by E. coli.…”

Section: Protein Quality Control and Characterization Of Mfasmentioning

confidence: 86%

Probing the Modularity of Megasynthases by Rational Engineering of a Fatty Acid Synthase (FAS) Type I

Rittner

Paithankar

Drexler

et al. 2018

Preprint

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Modularity is an aspect of a decomposable system with a coordinating authority that acts as a glue which holds the loosely held components. These multi-component entities ("modules") facilitate rewiring into different designs allowing for change. Such modular character is a fundamental property of many biological entities, especially the family of megasynthases such as polyketide synthases (PKSs). The ability of these PKSs to produce diverse product spectra is strongly coupled to their broad architectural modularity.Decoding the molecular basis of modularity, i.e. identifying the folds and domains that comprise the modules as well as understanding constrains of the assembly of modules, is of utmost importance for harnessing megasynthases for the synthesis of designer compounds. In this study, we exploit the close semblance between PKSs and animal FAS to re-engineer animal FAS to probe the modularity of the FAS/PKS family. Guided by structural and sequence information, we truncate and dissect animal FAS into its components, and reassemble them to generate new PKS-like modules as well as bimodular constructs. The novel engineered modules resemble all four common module types of PKSs and demonstrate that this approach can be a powerful tool to create higher catalytic efficiency. Our data exemplify the inherent plasticity and robustness of the overall FAS/PKS fold, and open new avenues to explore FAS-based biosynthetic pathways for custom compound design. 3 Keywords Multidomain protein, modularity of megasynthases, polyketide synthase, protein engineering Abbreviations FAS, fatty acid synthase; PKS, polyketide synthases; CMN, Corynebacteria,

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“…23 Also short chain fatty acids such as propionate and butyrate taken up from surrounding media can be converted to cognate acyl-CoA molecules with the catalysis of short chain acyl-CoA synthetases (ACS). 24,25 It is thus highly possible that isobutyryl-CoA can be synthesized from this pathway with isobutyrate as the source agent. Importantly, isobutyryl-CoA is a key intermediate of valine metabolism pathway so valine may also stimulate biosynthesis of isobutyryl-CoA (Figure 1).…”

Section: Cellular Metabolism Of Isobutyrate and Valine Lead To Isobutmentioning

confidence: 99%

Identification of Lysine Isobutyrylation as A New Histone Modification Mark

Zhu

Han

Halabelian

et al. 2020

Preprint

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Short-chain acylation of lysine residues in eukaryotic proteins are recognized as essential posttranslational chemical modifications (PTMs) that regulate cellular processes from transcription, cell cycle, metabolism, to signal transduction. Lysine butyrylation was initially discovered as a normal straight chain butyrylation (Knbu). Here we report its structural isomer, branched chain butyrylation, i.e. lysine isobutyrylation (Kibu), existing as a new PTM on nuclear histones. Uniquely, isobutyryl-CoA is derived from valine catabolism and branched chain fatty acid oxidation which is distinct from the metabolism of n-butyryl-CoA. Several histone acetyltransferases were found to possess lysine isobutyryltransferase activity, especially p300 and HAT1. We resolved the X-ray crystal structures of HAT1 in complex with isobutyryl-CoA that gleaned an atomic level insight into HAT-catalyzed isobutyrylation. RNA-Seq profiling revealed that isobutyrate greatly affected the expression of genes associated with many pivotal biological pathways. Our findings identify Kibu as a novel chemical modification mark in histones and suggest its extensive role in regulating epigenetics and cellular physiology.

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Production and utilization of butyryl-CoA by fatty acid synthetase from mammalian tissues

Cited by 25 publications

References 27 publications

Medium-chain fatty acid synthesis by goat mammary-gland fatty acid synthetase. The effect of limited proteolysis

Medium-chain fatty acid synthesis by goat mammary-gland fatty acid synthetase. The effect of limited proteolysis

Probing the Modularity of Megasynthases by Rational Engineering of a Fatty Acid Synthase (FAS) Type I

Identification of Lysine Isobutyrylation as A New Histone Modification Mark

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