Abstract
This review gives an overview of different yeast strains and enzyme classes involved in yeast whole-cell biotransformations. A focus was put on the synthesis of compounds for fine chemical and API (= active pharmaceutical ingredient) production employing single or only few-step enzymatic reactions. Accounting for recent success stories in metabolic engineering, the construction and use of synthetic pathways was also highlighted. Examples from academia and industry and advances in the field of designed yeast strain construction demonstrate the broad significance of yeast whole-cell applications. In addition to Saccharomyces cerevisiae, alternative yeast whole-cell biocatalysts are discussed such as Candida sp., Cryptococcus sp., Geotrichum sp., Issatchenkia sp., Kloeckera sp., Kluyveromyces sp., Pichia sp. (including Hansenula polymorpha = P. angusta), Rhodotorula sp., Rhodosporidium sp., alternative Saccharomyces sp., Schizosaccharomyces pombe, Torulopsis sp., Trichosporon sp., Trigonopsis variabilis, Yarrowia lipolytica and Zygosaccharomyces rouxii.
Highlights
Introduction of theErwinia uredovora galactose carotenoid biosynthesis genes [216]crtE, crtB, crtI and crtY (Æ b-carotene) and crtE, crtB and crtI (Æ lycopene), respectively, under the control ofS. cerevisiae promoters and terminators [221]
In the following we focus on engineered yeast platform strains for the production of mostly chiral precursors for the pharmaceutical, food or feed industry, thereby including single- and multi-step biocatalytic reactions
Two different routes were chosen, namely a propionylCoA-dependent and a propionyl-coenzyme A (CoA)-independent one. They achieved to demonstrate that the methylmalonyl-CoA, which was produced by the yeast strain, is further converted to a triketide lactone (Table 6 and Additional File 6, Entry 3). 0.5 to 1 mg/L of the triketide lactone were obtained with the propionyl-CoAdependent route
Summary
The advent of yeast whole-cell biocatalysis coincided with the development of first technologies for the human society. The strain Geotrichum candidum SC5469 was described to be employed by Bristol-Myers Squibb for the stereoselective reduction of 4-chloro-3-oxo-butanoic acid methyl ester to the corresponding (S)-3-hydroxyalcohol [74] This conversion yielded the product in 95% yield and 99% ee and provided a useful chiral building block, e.g. for the synthesis of a cholesterol antagonist that inhibits hydroxymethyl glutaryl CoA reductase [117,118]. Kratzer et al [158] succeeded in overcoming limitations of baker’s yeast in the asymmetric reduction of a-keto esters using a combinatorial approach They improved the enzyme by exchanging the amino acid residue tryptophane 23 with phenylalanine (CtXR-W23F) which resulted in an up to eightfold higher NADH-dependent activity compared to the wild-type enzyme employing a series of aromatic a-keto esters as substrates [159]. For the applications in human nutrition, several yeast strains will provide interesting alternatives due to their food-grade status
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