Biochemical Engineering of Natural Product Biosynthesis Pathways

Strohl, William R.

doi:10.1006/mben.2000.0172

Cited by 48 publications

(18 citation statements)

References 98 publications

(101 reference statements)

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“…The present work is a first step in utilizing that strategy as a natural source for constructing an efficient plant transformation system. In addition, this work uniquely grafted six genes related to the complex rhizobitoxine biosynthetic pathway (Yasuta et al , 2001; Okazaki et al , 2004b) into a different metabolic background ( Agrobacterium ) as a trial of metabolic engineering of plant‐associated bacteria (Strohl, 2001).…”

Section: Resultsmentioning

confidence: 99%

Rhizobitoxine production inAgrobacterium tumefaciensC58 byBradyrhizobium elkanii rtxACDEFGgenes

Sugawara

Haramaki

Nonaka

et al. 2007

FEMS Microbiology Letters

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We examined the genetic basis and transfer for production of rhizobitoxine, an inhibitor of ethylene biosynthesis in plants, directed by the rtx genes of Bradyrhizobium elkanii. Comparison with genome sequences of Bradyrhizobium japonicum and Xanthomonas oryzae suggests that the rtx genes extend from the previously identified rtxAC genes through four additional genes rtxDEFG. Reverse transcription-PCR analysis showed that the rtxACDEFG genes are expressed as an operon. Mutational analysis indicated that rtxDEG mutants reduced rhizobitoxine biosynthesis, while the rtxA gene is essential for its synthesis. Introduction of the rtxACDEFG into Agrobacterium tumefaciens resulted in strong expression of rtxACDEFG and production of RtxA protein, but no rhizobitoxine was detectable. Addition of O-acetylhomoserine, a precursor of rhizobitoxine, to the Agrobacterium derivative, however, fostered production of rhizobitoxine in culture. The diluted culture supernatant inhibited the activities of beta-cystathionase and 1-aminocyclopropane-1-carboxylate synthase, indicating that A. tumefaciens carrying rtxACDEFG genes excreted biologically active rhizobitoxine.

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Section: Resultsmentioning

confidence: 99%

Rhizobitoxine production inAgrobacterium tumefaciensC58 byBradyrhizobium elkanii rtxACDEFGgenes

Sugawara

Haramaki

Nonaka

et al. 2007

FEMS Microbiology Letters

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“…Traditional chemical companies have begun to develop infrastructures for the production of compounds by using biocatalytic processes (1)(2)(3). Considerable progress has been reported toward new processes for commodity chemicals such as ethanol (4,5), lactic acid (6-8), 1,3-propanediol (9,10), and adipic acid (11).…”

mentioning

confidence: 99%

Engineering Escherichia coli for efficient conversion of glucose to pyruvate

Causey

Shanmugam

Yomano

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

238

168

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Escherichia coli TC44, a derivative of W3110, was engineered for the production of pyruvate from glucose by combining mutations to minimize ATP yield, cell growth, and CO2 production (⌬atpFH ⌬adhE ⌬sucA) with mutations that eliminate acetate production [poxB::FRT (FLP recognition target) ⌬ackA] and fermentation products (⌬focA-pflB ⌬frdBC ⌬ldhA ⌬adhE). In mineral salts medium containing glucose as the sole carbon source, strain TC44(⌬focA-pflB ⌬frdBC ⌬ldhA ⌬atpFH ⌬adhE ⌬sucA poxB::FRT ⌬ackA) converted glucose to pyruvate with a yield of 0.75 g of pyruvate per g of glucose (77.9% of theoretical yield; 1.2 g of pyruvate liters ؊1 ⅐h ؊1 ). A maximum of 749 mM pyruvate was produced with excess glucose. Glycolytic flux was >50% faster for TC44 producing pyruvate than for the wild-type W3110 during fully aerobic metabolism. The tolerance of E. coli to such drastic changes in metabolic flow and energy production implies considerable elasticity in permitted pool sizes for key metabolic intermediates such as pyruvate and acetyl-CoA. In strain TC44, pyruvate yield, pyruvate titer, and the rate of pyruvate production in mineral salts medium were equivalent or better than previously reported for other biocatalyts (yeast and bacteria) requiring complex vitamin feeding strategies and complex nutrients. TC44 offers the potential to improve the economics of pyruvate production by reducing the costs of materials, product purification, and waste disposal.metabolic engineering ͉ glycolytic flux ͉ fermentation ͉ ATPase

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“…At least five different classes of genes control metabolite production (Malik, 1979): (i) structural genes coding for product synthases, (ii) regulatory genes determining the onset and expression of structural genes, (iii) resistance genes determining the resistance of the producer to its own antibiotic, (iv) permeability genes regulating entry, exclusion and excretion of the product, and (v) regulatory genes controlling pathways providing precursors and cofactors. Overproduction of microbial metabolites is effected by (i) increasing precursor pools, (ii) adding, modifying or deleting regulatory genes, (iii) altering promoter, terminator and/or regulatory sequences, (iv) increasing copy number of genes encoding enzymes catalyzing bottleneck reactions, and (v) removing competing unnecessary pathways (Strohl, 2001).…”

Section: Applications Of Mutationmentioning

confidence: 99%

Genetic improvement of processes yielding microbial products

2006

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Although microorganisms are extremely good in presenting us with an amazing array of valuable products, they usually produce them only in amounts that they need for their own benefit; thus, they tend not to overproduce their metabolites. In strain improvement programs, a strain producing a high titer is usually the desired goal. Genetics has had a long history of contributing to the production of microbial products. The tremendous increases in fermentation productivity and the resulting decreases in costs have come about mainly by mutagenesis and screening/selection for higher producing microbial strains and the application of recombinant DNA technology.

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Biochemical Engineering of Natural Product Biosynthesis Pathways

Cited by 48 publications

References 98 publications

Rhizobitoxine production inAgrobacterium tumefaciensC58 byBradyrhizobium elkanii rtxACDEFGgenes

Rhizobitoxine production inAgrobacterium tumefaciensC58 byBradyrhizobium elkanii rtxACDEFGgenes

Engineering Escherichia coli for efficient conversion of glucose to pyruvate

Genetic improvement of processes yielding microbial products

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