Rational Engineering of (S)-Norcoclaurine Synthase for Efficient Benzylisoquinoline Alkaloids Biosynthesis

• Type: Article in International Scientific Journal
• Date: 2023

Authors

De Sousa, JPM (Author) Other; Oliveira, NCSA (Author) Other; Pedro A Fernandes (Author) FCUP

Journal

Title: Molecules

Serial No. 9 Vol. 23 No. 2288

Final page: 4265

ISSN: 1420-3049

Publisher: MDPI

Other information

Authenticus ID: P-00Y-FQT

DOI: 10.3390/molecules28114265

Abstract (EN): <jats:p>(S)-Norcoclaurine is synthesized in vivo through a metabolic pathway that ends with (S)-norcoclaurine synthase (NCS). The former constitutes the scaffold for the biosynthesis of all benzylisoquinoline alkaloids (BIAs), including many drugs such as the opiates morphine and codeine and the semi-synthetic opioids oxycodone, hydrocodone, and hydromorphone. Unfortunately, the only source of complex BIAs is the opium poppy, leaving the drug supply dependent on poppy crops. Therefore, the bioproduction of (S)-norcoclaurine in heterologous hosts, such as bacteria or yeast, is an intense area of research nowadays. The efficiency of (S)-norcoclaurine biosynthesis is strongly dependent on the catalytic efficiency of NCS. Therefore, we identified vital NCS rate-enhancing mutations through the rational transition-state macrodipole stabilization method at the Quantum Mechanics/Molecular Mechanics (QM/MM) level. The results are a step forward for obtaining NCS variants able to biosynthesize (S)-norcoclaurine on a large scale.</jats:p>

Language: English

Type (Professor's evaluation): Scientific