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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2023

Autores

De Sousa, JPM (Autor) Outra; Oliveira, NCSA (Autor) Outra; Pedro A Fernandes (Autor) FCUP

Revista

Título: Molecules

Nº de Série 9 Vol. 23 Nº 2288

Página Final: 4265

ISSN: 1420-3049

Editora: MDPI

Outras Informações

ID Authenticus: 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>

Idioma: Inglês

Tipo (Avaliação Docente): Científica