Scholarlink

<p>Flavonoids and stilbenes are phenylpropanoid-derived secondary metabolites found in plants, fungi, and microorganisms. They serve important physiological functions and offer a range of pharmacological benefits, including antioxidant, anti-inflammatory, anticancer, and antimicrobial effects. However, many native flavonoids and stilbenes have limited pharmacology and industrial use due to poor bioavailability and low metabolic stability. O-methylation is a key post-biosynthetic modification that improves the physicochemical and pharmacokinetic properties of these compounds. This process, catalyzed by S-adenosyl-L-methionine [SAM]-dependent <i>O</i>-methyltransferases [OMTs], increases lipophilicity, chemical stability, and membrane permeability, often resulting in greater bioactivity. As a result, methylated derivatives such as sakuranetin, acacetin, isorhamnetin, and pterostilbene frequently show enhanced therapeutic efficacy, even though they are less abundant in nature. Advances in metabolic engineering and synthetic biology have enabled efficient biosynthesis of methylated flavonoids and stilbenes in microbial hosts such as <i>Escherichia coli</i>, <i>Saccharomyces cerevisiae</i>, and <i>Streptomyces</i> species. Strategies including pathway optimization, SAM regeneration, enzyme engineering, and CRISPR-based genome editing have significantly improved production yields and regioselectivity, with some systems surpassing native producers. Despite this progress, challenges remain in enzyme specificity, metabolic bottlenecks, and downstream processing. This review summarizes recent developments in understanding methylation biosynthetic pathways, OMT diversity, and microbial engineering strategies. It also highlights the pharmacological significance of methylation and the potential of engineered microbial platforms for sustainable, scalable production of methylated flavonoids and stilbenes for pharmaceutical and nutraceutical use.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Metabolic Engineering for Biotechnological Production of Bioactive Methylated Flavonoids and Stilbenes: Progress and Perspectives

  • 期刊论文

  • 发表日期：

    2026年4月11日

查看全文
  • Santosh Kumar Shrestha,
  • Tae-Jin Oh

摘要

Flavonoids and stilbenes are phenylpropanoid-derived secondary metabolites found in plants, fungi, and microorganisms. They serve important physiological functions and offer a range of pharmacological benefits, including antioxidant, anti-inflammatory, anticancer, and antimicrobial effects. However, many native flavonoids and stilbenes have limited pharmacology and industrial use due to poor bioavailability and low metabolic stability. O-methylation is a key post-biosynthetic modification that improves the physicochemical and pharmacokinetic properties of these compounds. This process, catalyzed by S-adenosyl-L-methionine [SAM]-dependent O-methyltransferases [OMTs], increases lipophilicity, chemical stability, and membrane permeability, often resulting in greater bioactivity. As a result, methylated derivatives such as sakuranetin, acacetin, isorhamnetin, and pterostilbene frequently show enhanced therapeutic efficacy, even though they are less abundant in nature. Advances in metabolic engineering and synthetic biology have enabled efficient biosynthesis of methylated flavonoids and stilbenes in microbial hosts such as Escherichia coli, Saccharomyces cerevisiae, and Streptomyces species. Strategies including pathway optimization, SAM regeneration, enzyme engineering, and CRISPR-based genome editing have significantly improved production yields and regioselectivity, with some systems surpassing native producers. Despite this progress, challenges remain in enzyme specificity, metabolic bottlenecks, and downstream processing. This review summarizes recent developments in understanding methylation biosynthetic pathways, OMT diversity, and microbial engineering strategies. It also highlights the pharmacological significance of methylation and the potential of engineered microbial platforms for sustainable, scalable production of methylated flavonoids and stilbenes for pharmaceutical and nutraceutical use.