The crystal structure of β-ketoacyl-acyl carrier protein synthase II from Synechocystis sp. at 1.54 Å resolution and its relationship to other condensing enzymes11Edited by R. Huber

Moche, M.; Dehesh, Katayoon; Edwards, Patricia C.; Lindqvist, Ylva

doi:10.1006/jmbi.2000.4272

Cited by 70 publications

(69 citation statements)

References 43 publications

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“…DVU1204 encodes 3-oxoacyl-(acyl-carrierprotein) synthase II FabF (also named as betaketoacyl-ACP synthase II), which has been shown Genetic basis of salt adaptation in D. vulgaris A Zhou et al to function in fatty acid biosynthesis in Synechocystis (Moche et al, 2001) as well as the synthesis of both unsaturated fatty acids and saturated fatty acids in Clostridium (Zhu et al, 2009). The DvH genome lacks unsaturated fatty acids biosynthesis genes fabA and fabB (Campbell and Cronan, 2001); but increased percentages of unsaturated fatty acids have been observed in evolved strains ES9-11 and EC3-10 ( Zhou et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Rapid selective sweep of pre-existing polymorphisms and slow fixation of new mutations in experimental evolution of Desulfovibrio vulgaris

Zhou

Hillesland

et al. 2015

The ISME Journal

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To investigate the genetic basis of microbial evolutionary adaptation to salt (NaCl) stress, populations of Desulfovibrio vulgaris Hildenborough (DvH), a sulfate-reducing bacterium important for the biogeochemical cycling of sulfur, carbon and nitrogen, and potentially the bioremediation of toxic heavy metals and radionuclides, were propagated under salt stress or non-stress conditions for 1200 generations. Whole-genome sequencing revealed 11 mutations in salt stress-evolved clone ES9-11 and 14 mutations in non-stress-evolved clone EC3-10. Whole-population sequencing data suggested the rapid selective sweep of the pre-existing polymorphisms under salt stress within the first 100 generations and the slow fixation of new mutations. Population genotyping data demonstrated that the rapid selective sweep of pre-existing polymorphisms was common in salt stress-evolved populations. In contrast, the selection of pre-existing polymorphisms was largely random in EC populations. Consistently, at 100 generations, stress-evolved population ES9 showed improved salt tolerance, namely increased growth rate (2.0-fold), higher biomass yield (1.8-fold) and shorter lag phase (0.7-fold) under higher salinity conditions. The beneficial nature of several mutations was confirmed by site-directed mutagenesis. All four tested mutations contributed to the shortened lag phases under higher salinity condition. In particular, compared with the salt tolerance improvement in ES9-11, a mutation in a histidine kinase protein gene lytS contributed 27% of the growth rate increase and 23% of the biomass yield increase while a mutation in hypothetical gene DVU2472 contributed 24% of the biomass yield increase. Our results suggested that a few beneficial mutations could lead to dramatic improvements in salt tolerance.

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Section: Discussionmentioning

confidence: 99%

Rapid selective sweep of pre-existing polymorphisms and slow fixation of new mutations in experimental evolution of Desulfovibrio vulgaris

Zhou

Hillesland

et al. 2015

The ISME Journal

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“…It is interesting to note that some members belonging to the thiolase fold family possess the capability to use long aliphatic chains as substrates (15,36,37). The analysis of the three-dimensional crystal structure of KAS III enzyme (1HZP) from M. tuberculosis (referred to as mtFabH) has revealed the mechanism by which it can catalyze the decarboxylative condensation of bulky myristoyl-CoA with malonyl-acyl carrier protein.…”

Section: Figmentioning

confidence: 99%

“…The three-dimensional crystal structures of CHS from Medicago sativa (alfalfa) (12) and 2PS from Gerbera hybrida (daisy) (13) have led to a more comprehensive understanding to structurally rationalize the mechanistic differences between enzymes within the thiolase family. Presently, the thiolase fold enzymes can be grouped into three families (11,14,15). ␤-Ketoacyl acyl carrier protein synthase (KAS) I and KAS II proteins comprise one group, and KAS III and type III PKS form another group.…”

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confidence: 99%

A New Family of Type III Polyketide Synthases in Mycobacterium tuberculosis

Saxena

Yadav²,

Mohanty

et al. 2003

Journal of Biological Chemistry

105

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The Mycobacterium tuberculosis genome has revealed a remarkable array of polyketide synthases (PKSs); however, no polyketide product has been isolated thus far. Most of the PKS genes have been implicated in the biosynthesis of complex lipids. We report here the characterization of two novel type III PKSs from M. tuberculosis that are involved in the biosynthesis of long-chain ␣-pyrones. Measurement of steady-state kinetic parameters demonstrated that the catalytic efficiency of PKS18 protein was severalfold higher for long-chain acyl-coenzyme A substrates as compared with the smallchain precursors. The specificity of PKS18 and PKS11 proteins toward long-chain aliphatic acyl-coenzyme A (C 12 to C 20 ) substrates is unprecedented in the chalcone synthase (CHS) family of condensing enzymes. Based on comparative modeling studies, we propose that these proteins might have evolved by fusing the catalytic machinery of CHS and ␤-ketoacyl synthases, the two evolutionarily related members with conserved thiolase fold. The mechanistic and structural importance of several active site residues, as predicted by our structural model, was investigated by performing site-directed mutagenesis. The functional identification of diverse catalytic activity in mycobacterial type III PKSs provide a fascinating example of metabolite divergence in CHSlike proteins.Mycobacteria are classified in the phylogeny of the Actinomycetes, along with the Streptomyces bacteria. Interestingly, these two actinomycete genera have received immense attention due to their contrasting effects on human society. Whereas Streptomyces have provided a rich source of antibiotics and other therapeutic products for human diseases, Mycobacterium tuberculosis and Mycobacterium leprae have been two of humankind's greatest scourges. Although the original phylogenic classifications of Mycobacterium and Streptomyces were based primarily on morphology, the genome sequences of these organisms have further established their common lineage (1, 2). These genome sequences have revealed several families of genes that are common between them, which include an unusually large number of gene clusters that are homologous to polyketide synthases (PKSs). 1 Although a polyketide producthas not yet been isolated from M. tuberculosis, recent studies have implicated some of its PKS genes in the biosynthesis of complex lipids (3). In this report, we have characterized two novel polyketide synthases from M. tuberculosis, which are involved in the biosynthesis of unusual long-chain ␣-pyrones.Polyketides are a diverse class of secondary metabolites that possess a broad range of biological activities (4). Despite structural diversity of these natural products, PKSs synthesize polyketides by a common chemical strategy. Initial priming by a starter molecule is followed by repetitive decarboxylative condensation of coenzyme A (CoA) analogues of simple carboxylic acids. PKS elongates the polyketide chain either by repetitively using a single active site to perform multiple condensation reaction...

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“…Thus far, the fabA and fabB genes are restricted to the alpha-and gamma-proteobacteria, and it remains a mystery how most other organisms capable of anaerobic growth (e.g., clostridia) make unsaturated fatty acids. In contrast, FabF homologues are found throughout the bacteria and are considered the generic KAS of long-chain fatty acid synthesis (7,23,31). However, members of the Pasteurellaceae of gamma-proteobacteria lack a FabF homologue recognizable by sequence alignments.…”

mentioning

confidence: 99%

“…Moreover, the sequence distinctions between genes encoding FabB versus those encoding FabF are based only on gross alignments, not on the conservation (or lack of conservation) of residues known to be responsible for the differing substrate specificities that the E. coli enzymes display in vivo. Indeed, despite the fact that we have high-resolution-X-ray crystal structures of both the E. coli FabB and FabF proteins, the structural basis of the differing specificities of the two enzymes remains unclear (27,31,32,34,35). Therefore, it may be possible for a FabB protein to gain the specificity of FabF by undergoing only a few mutational alterations.…”

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confidence: 99%

Haemophilus influenzae Rd Lacks a Stringently Conserved Fatty Acid Biosynthetic Enzyme and Thermal Control of Membrane Lipid Composition

Wang¹,

Cronan

2003

J Bacteriol

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The organization of the fatty acid synthetic genes of Haemophilus influenzae Rd is remarkably similar to that of the paradigm organism, Escherichia coli K-12, except that no homologue of the E. coli fabF gene is present. This finding is unexpected, since fabF is very widely distributed among bacteria and is thought to be the generic 3-ketoacyl-acyl carrier protein (ACP) synthase active on long-chain-length substrates. However, H. influenzae Rd contains a homologue of the E. coli fabB gene, which encodes a 3-ketoacyl-ACP synthase required for unsaturated fatty acid synthesis, and it seemed possible that the H. influenzae FabB homologue might have acquired the functions of FabF. E. coli mutants lacking fabF function are unable to regulate the compositions of membrane phospholipids in response to growth temperature. We report in vivo evidence that the enzyme encoded by the H. influenzae fabB gene has properties essentially identical to those of E. coli FabB and lacks FabF activity. Therefore, H. influenzae grows without FabF function. Moreover, as predicted from studies of the E. coli fabF mutants, H. influenzae is unable to change the fatty acid compositions of its membrane phospholipids with growth temperature. We also demonstrate that the fabB gene of Vibrio cholerae El Tor N16961 does not contain a frameshift mutation as was previously reported.The fatty acid synthetic pathway of Escherichia coli has provided a very successful model for fatty acid synthesis in bacteria and plant chloroplasts (13, 38). Indeed, not only are the sequences of the E. coli fatty acid synthetic proteins highly conserved in other bacteria, but surprisingly, in many cases the arrangements of the genes encoding the synthetic enzymes are also conserved. As discussed elsewhere (7), the major exception to the E. coli paradigm is in the synthesis of unsaturated fatty acids. In E. coli, synthesis of the normal fatty acid content requires three enzymes, the products of the fabA, fabB, and fabF genes. FabA is the key enzyme of the classic anaerobic pathway of unsaturated fatty acid synthesis (2) and introduces the cis (or Z) double bond into a 10-carbon intermediate (Fig.

show abstract

The crystal structure of β-ketoacyl-acyl carrier protein synthase II from Synechocystis sp. at 1.54 Å resolution and its relationship to other condensing enzymes11Edited by R. Huber

Cited by 70 publications

References 43 publications

Rapid selective sweep of pre-existing polymorphisms and slow fixation of new mutations in experimental evolution of Desulfovibrio vulgaris

Rapid selective sweep of pre-existing polymorphisms and slow fixation of new mutations in experimental evolution of Desulfovibrio vulgaris

A New Family of Type III Polyketide Synthases in Mycobacterium tuberculosis

Haemophilus influenzae Rd Lacks a Stringently Conserved Fatty Acid Biosynthetic Enzyme and Thermal Control of Membrane Lipid Composition

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