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Table 6 Synthetic pathways for polyketide and flavonoid synthesis

From: Yeast cell factories for fine chemical and API production

Host organism

Engineering steps

Substrate

Product/Outcome

Ref

Saccharomyces cerevisiae

1) Introduction of the Penicillium patulum PKS 6-MSASI gene

YPD (+ glucose)

1.7 g/L (2-fold more than by natural host Penicillium patulum)

[232]

 

2) Overexpression of the Bacillus subtilis surfactin P-pantII transferase (Sfp) gene

    

Saccharomyces cerevisiae

1) Introduction of the Penicillium patulum PKS 6-MSASI gene

galactose minimal medium

> 200 mg/L for strain expressing the PPTaseII from A. nidulans

[231]

 

2) Introduction of the surfactin P-pantII transferase gene from Bacillus subtilis (sfp) or from Aspergillus nidulans (npgA)

    

Saccharomyces cerevisiae BJ5464 (protease deficient)

1) Introduction of pathways for methylmalonyl-coenzyme A production:

YPD (+ glucose) + propionate and propyl-diketide thioester feed

0.5–1 mg/L with propionyl-CoA-dependent route (PCC-pathway)

[215]

 

Propionyl-CoA-dependent route:

    
 

+ Salmonella typhimurium propionyl-CoA synthetase

    
 

+ Streptomyces coelicolor propionyl-CoA carboxylase pathway (PCC)

    
 

Propionyl-CoA-independent route

    
 

+ Streptomyces coelicolor malonyl/methylmalonyl-CoA ligase pathway (MatB)

    
 

2) Expression of module 2 from DEBS1III linked to the thioesterase domain (TE) of DEBS3 [243, 244]

    
 

3) Co-expression of five tRNA genes E4, R2, L5, Q2 and P2 [245]

    

Saccharomyces cerevisiae

1) Introduction of the Populus trichocarpa X Populus deltoides (= poplar) cDNAs encoding:

selective, synthetic medium supplemented with glucose and galactose, respectively

~3–10 mg/L triple-expressing strains (PAL2/C4H/CPR2 and PAL4/C4H/CPR2, respectively; with slight advantages for the PAL2 expressing strain)

[233]

 

+ Phenylalanine ammonia lyase (isoform PAL2 and PAL4, respectively)

feed with [3H]phenylalanine [14C]cinnamate

   
 

+ Cinnamate 4-hydroxylase (C4H)

    
 

+ Cytochrome P450 reductase (CPR2)

    

Saccharomyces cerevisiae

1) Introduction of the Helianthus tuberosus C4H Cytochrome P-450 and H. tuberosus NADPH-Cytochrome P-450 reductase

glucose or raffinose addition of L-phenylalanine (1.0 mM)

after 24 h:

[234]

 

2) Introduction of the Rhodotorula glutinis ATCC 10788 phenylalanine ammonia-lyase (PAL)

induction with galactose

 

on glucose: 354 μM (→ 58 mg/L)

 
    

on raffinose: 498 μM (→ 82 mg/L)

 

Saccharomyces cerevisiae AH22

1) Introduction of the phenylpropanoid pathway:

YPD (+ glucose) and YPL (+ galactose)

S. cerevisiae AH22 with PAL, 4CL and CHS produced ~7 mg/L of naringenin and 0.8 mg/L of pinocembrin

 

[235]

 

- Rhodosporidium toruloides phenylalanine ammonia lyase (PAL)

    
 

- Arabidopsis thaliana 4-coumarate:coenzyme A (CoA) ligase (4CL)

    
 

- Hypericum androsaemum chalcone synthase (CHS)

    

Saccharomyces cerevisiae YPH499

1) Introduction of the chalcone synthase (CHS) from ripe raspberry (Rubus idaeus) or a variant thereof (CHS L214I-F215L)

YPGal-medium (induction with galactose)

raspberry fruit: 1–4 mg/kg

[237]

 

2) Introduction of the tobacco 4-coumarate-coenzyme A ligase (4CL)

addition of p-coumaric acid (3 mM)

 

recombinant E. coli: 5 mg/L

[236]

    

recombinant S. cerevisiae: no proper detection of raspberry ketone

[236]

Saccharomyces cerevisiae FY23

1) Introduction of the coenzyme-A ligase 4CL216 gene from hybrid poplar under the control of the yeast ADH2 gene promoter and terminator (→ CAL1) and

SCDL-medium (0.67% yeast nitrogen base, 0.8% glucose and required growth factors) with 10 mg/L p-coumaric acid

recombinant S. cerevisiae: ~1.5 μg/L

 

[238]

 

2) the resveratrol synthase (VST1) from grapevine (Vitis vinifera)

    

Saccharomyces cerevisiae CEN.PK 113-3b (ura3 his3)

1) Introduction of the 4-coumarate: coenzyme A (CoA) ligase (4CL2 gene – GenBank accession no. U50846) from Nicotiana tabacum cv. Samsun

50 mL yeast nitrogen base medium supplemented with 5 mM p-coumaric acid and 2% galactose to induce gene expression

S. cerevisiae: ~6 mg/L

[239]

 

2) Introduction of the STS gene from Vitis vinifera encoding for the stilbene synthase (STS)

  

recomb. E. coli expressing the same enzymes: ~16 mg/L

 
  1. IPKS = polyketide synthase; 6-MSAS = 6-methylsalicylic acid synthase
  2. IIPPTase = P-pant transferase = 4'-phophopantetheinyl transferase
  3. IIIDEBS = deoxyerythronolide B synthase from Saccharopolyspora erythraea, a typical 'modular' polyketide synthase.