Transcriptome-Guided Identification of N-Acetyltransferases Involved in Melatonin Biosynthesis in a...

Area of Science:

• Microbial Biotechnology
• Synthetic Biology
• Biochemistry

Background:

• Melatonin is a neurohormone with increasing demand in pharmaceuticals and supplements.
• Microbial production offers a sustainable alternative to chemical synthesis for melatonin.
• Engineered microbial systems are crucial for efficient biosynthesis of valuable compounds.

Purpose of the Study:

• To identify endogenous N-acetyltransferases involved in melatonin biosynthesis in engineered Streptomyces albus.
• To improve melatonin production through genetic engineering of the biosynthetic pathway.
• To expand the utility of bacterial N-acyltransferases in synthetic biology.

Main Methods:

• Transcriptome-guided mining to identify key enzymes in melatonin biosynthesis.
• Genetic engineering of Streptomyces albus, including enhancing decarboxylase expression and deleting specific N-acetyltransferases.
• Fermentation and quantification of melatonin production in engineered strains.

Main Results:

• Identified three key N-acetyltransferases with distinct substrate specificities in melatonin biosynthesis.
• Developed an improved Streptomyces albus strain with enhanced melatonin production.
• Achieved approximately 380 mg/L of melatonin, a ~65% increase compared to the parental strain.

Conclusions:

• This study successfully advanced microbial melatonin biosynthesis through enzyme identification and pathway optimization.
• The engineered N-acetyltransferases have potential applications in synthetic biology for diverse microbial hosts.
• Enhanced microbial production of melatonin provides a sustainable route for pharmaceutical and supplement industries.