MICROORGANISMS FOR EFFICIENT PRODUCTION OF MELATONIN AND RELATED COMPOUNDS

摘要

Recombinant microbial cells and methods for producing 5HTP, melatonin and related compounds using such cells are described. More specifically, the recombinant microbial cell may comprise exogenous genes encoding one or more of an L-tryptophan hydroxylase, a 5-hydroxy-L-tryptophan decarboxylyase, a serotonin acetyltransferase, an acetylserotonin O-methyltransferase; and means for providing tetrahydrobiopterin (THB), and can be further genetically modified to enrich one or more of tryptophan, S-adenosyl-L-methinonine and acetyl coenzyme A. Related sequences and vectors for use in preparing such recombinant microbial cells are also described.

主权项

1. A recombinant microbial cell comprising exogenous nucleic acid sequences encoding an L-tryptophan hydroxylase (TPH) (EC 1.14.16.4), a 5-hydroxy-L-tryptophan decarboxylase (DDC) (EC 4.1.1.28), a serotonin acetyltransferase (AANAT) (EC 2.3.1.87 or EC 2.3.1.5), an acetylserotonin O-methyltransferase (ASMT) (EC 2.1.1.4), and enzymes providing at least one pathway for producing tetrahydrobiopterin (THB), wherein the recombinant microbial cell
(i) further comprises a genetic modification providing for an increase in S-adenosyl-L-methinonine (SAM) production, an increase in acetyl coenzyme A (AcCoA) production, an increase in tryptophan production, or a combination of any thereof; and/or (ii) comprises an exogenous nucleic acid sequence encoding a TPH which comprises SEQ ID NO:177, SEQ ID NO:176, or functionally active variant, homolog or fragment of any thereof.