Fig. 3: De novo synthesis of substituted tetrahydroisoquinolines in strains engineered for (S)-norcoclaurine production.
From: A yeast platform for high-level synthesis of tetrahydroisoquinoline alkaloids
a Formation of salsolinol (13) from acetaldehyde (12) and dopamine (2) occurs spontaneously in yeast strains engineered for dopamine production. b NCS-catalyzed formation of substituted THIQs through catabolism of endogenous amino acids via the Ehrlich pathway. Amino acids are converted to the respective aldehyde species via sequential transamination (Aro8/Aro9) and decarboxylation (Aro10) reactions. In the presence of dopamine (2) and NCS, aldehydes are converted to the corresponding substituted THIQs. Stereochemistry of non-canonical substituted THIQs is omitted. c Relative levels of substituted THIQs in yeast strains engineered for (S)-norcoclaurine (3) production. Strain 1373 possesses the dopamine pathway and lacks an NCS biosynthetic enzyme. Refer to Fig. 1b and Supplementary Data 3 for genotypes of engineered strains. All of the depicted substituted THIQs were synthesized de novo by strain LP295 and all subsequent engineered strains. Error bars represent the mean ± s.d. of n = 3 independent biological samples. Asterisk (*) denotes a significant increase or decrease (P < 0.05) in product titer relative to the precursor strain. Statistical differences between control and derivative strains were tested using two-tailed Student’s t-test. 4-HPAA 4-hydroxyphenylacetaldehyde, IAA indole acetaldehyde, 3-MB 3-methylbutanal, PAA phenylacetaldehyde, spont. spontaneous. Source data underlying Fig. 3c are provided in a Source Data file.
