Thiamin-Diphosphate-Dependent Enzymes: New Aspects of Asymmetric CC Bond Formation

Pohl, Martina; Lingen, Bettina; Müller, Michael

doi:10.1002/1521-3765(20021202)8:23<5288::aid-chem5288>3.0.co;2-f

Cited by 160 publications

(69 citation statements)

References 22 publications

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“…Under the conditions tested, the use of wild-type E. coli expressing the same PDC produced no detectable L-PAC (43). In addition to PDC, other enzymes capable of catalyzing chiral carboligations of aldehyde substrates have been discussed (57). A similar challenge of limiting unwanted flux from aldehyde intermediates to alcohol byproducts has been encountered in the context of alkane production.…”

Section: Enhancing Bioconversion Of Aldehydes To Other Chemical Classesmentioning

confidence: 99%

Microbial Engineering for Aldehyde Synthesis

Kunjapur

Prather

2015

Appl Environ Microbiol

145

129

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Aldehydes are a class of chemicals with many industrial uses. Several aldehydes are responsible for flavors and fragrances present in plants, but aldehydes are not known to accumulate in most natural microorganisms. In many cases, microbial production of aldehydes presents an attractive alternative to extraction from plants or chemical synthesis. During the past 2 decades, a variety of aldehyde biosynthetic enzymes have undergone detailed characterization. Although metabolic pathways that result in alcohol synthesis via aldehyde intermediates were long known, only recent investigations in model microbes such as Escherichia coli have succeeded in minimizing the rapid endogenous conversion of aldehydes into their corresponding alcohols. Such efforts have provided a foundation for microbial aldehyde synthesis and broader utilization of aldehydes as intermediates for other synthetically challenging biochemical classes. However, aldehyde toxicity imposes a practical limit on achievable aldehyde titers and remains an issue of academic and commercial interest. In this minireview, we summarize published efforts of microbial engineering for aldehyde synthesis, with an emphasis on de novo synthesis, engineered aldehyde accumulation in E. coli, and the challenge of aldehyde toxicity.

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Section: Enhancing Bioconversion Of Aldehydes To Other Chemical Classesmentioning

confidence: 99%

Microbial Engineering for Aldehyde Synthesis

Kunjapur

Prather

2015

Appl Environ Microbiol

145

129

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“…These correlations are also visible in Figure 2-4, where too high estimates for k cat mostly come along with too high estimates for K iQ and K mA and vice versa. For this reason, optimal experiments should be designed in order to decrease this correlation and to improve the statistical significance of the parameter estimates (Duggleby and Clarke, 1991;Lindner and Hitzmann, 2006;Marquardt, 2005 (Demir et al, 2001b;Iding et al, 2000;Pohl et al, 2002). This formation of carbon-carbon bonds constitutes one of the key transformations in synthetic organic chemistry (Faber and Kroutil, 2005;Woodley, 2008).…”

Section: Comparison Of Computer Programsmentioning

confidence: 99%

“…Thiamin diphosphate (ThDP)-dependent enzymes catalyze carboligase reactions with an enantiomeric excess above 99% (Demir et al, 2001b;Iding et al, 2000;Pohl et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Model-based experimental analysis of enzyme kinetics in aqueous–organic biphasic systems

Zavrel

Schmidt

Michalik

et al. 2007

Journal of Biotechnology

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“…In contrast, the growth of strain CF seems not to require thiamine addition (Figure 1c). TDP is the cofactor of pyruvate-flavodoxin oxidoreductase and 2-oxoglutarate decarboxylase, two important carboxylases in central metabolism (Figure 3; Pohl et al, 2002). To test whether strain CF can synthesize TDP from thiamine, cultures of strain CF and E. coli grown on thiamine-containing medium (25 μg l -1 ) were harvested for intracellular thiamine derivatives analysis.…”

Section: Thiamine Biosynthesis and Metabolismmentioning

confidence: 99%

Refined experimental annotation reveals conserved corrinoid autotrophy in chloroform-respiring Dehalobacter isolates

et al. 2016

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Two novel chlorinated alkane-respiring Dehalobacter restrictus strains CF and DCA were isolated from the same enrichment culture, ACT-3, and characterized. The closed genomes of these highly similar sister strains were previously assembled from metagenomic sequence data and annotated. The isolation of the strains enabled experimental verification of predicted annotations, particularly focusing on irregularities or predicted gaps in central metabolic pathways and cofactor biosynthesis. Similar to D. restrictus strain PER-K23, strains CF and DCA require arginine, histidine and threonine for growth, although the corresponding biosynthesis pathways are predicted to be functional. Using strain CF to experimentally verify annotations, we determined that the predicted defective serine biosynthesis pathway can be rescued with a promiscuous serine hydroxymethyltransferase. Strain CF grew without added thiamine although the thiamine biosynthesis pathway is predicted to be absent; intracellular thiamine diphosphate, the cofactor of carboxylases in central metabolism, was not detected in cell extracts. Thus, strain CF may use amino acids to replenish central metabolites, portending entangled metabolite exchanges in ACT-3. Consistent with annotation, strain CF possesses a functional corrinoid biosynthesis pathway, demonstrated by increasing corrinoid content during growth and guided cobalamin biosynthesis in corrinoid-free medium. Chloroform toxicity to corrinoid-producing methanogens and acetogens may drive the conservation of corrinoid autotrophy in Dehalobacter strains. Heme detection in strain CF cell extracts suggests the 'archaeal' heme biosynthesis pathway also functions in anaerobic Firmicutes. This study reinforces the importance of incorporating enzyme promiscuity and cofactor availability in genome-scale functional predictions and identifies essential nutrient interdependencies in anaerobic dechlorinating microbial communities.

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Thiamin-Diphosphate-Dependent Enzymes: New Aspects of Asymmetric CC Bond Formation

Cited by 160 publications

References 22 publications

Microbial Engineering for Aldehyde Synthesis

Microbial Engineering for Aldehyde Synthesis

Model-based experimental analysis of enzyme kinetics in aqueous–organic biphasic systems

Refined experimental annotation reveals conserved corrinoid autotrophy in chloroform-respiring Dehalobacter isolates

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