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Thách thức và cơ hội trong quy trình sinh học sản xuất 5-aminolevulinic acid bằng cách sử dụng kỹ thuật di truyền và chuyển hóa: một bài tổng quan phê phán
Tóm tắt
Axít 5-aminolevulinic (5-ALA), một axít amin năm carbon không phải protein, đã nhận được sự chú ý đáng kể trong y học do việc được Cục Quản lý Thực phẩm và Dược phẩm Hoa Kỳ (FDA) phê duyệt cho việc chẩn đoán và điều trị ung thư dưới dạng liệu pháp quang động. Do việc tổng hợp hóa học 5-ALA có hiệu suất thấp, quy trình phức tạp và chi phí cao, nên sinh tổng hợp 5-ALA thông qua con đường C4 (còn gọi là con đường Shemin) và con đường C5 liên quan đến sự sinh tổng hợp heme trong vi sinh vật cho nhiều lợi thế hơn. Trong con đường C4, 5-ALA được hình thành từ phản ứng ngưng tụ của succinyl-CoA và glycine nhờ vào enzyme tổng hợp axít 5-aminolevulinic (ALAS) với pyridoxal phosphate (PLP) đóng vai trò là đồng yếu tố trong quá trình chuyển hóa sinh học một bước. Con đường C5 liên quan đến ba enzyme bao gồm glutamyl-tRNA synthetase (GltX), glutamyl-tRNA reductase (HemA), và glutamate-1-semialdehyde aminotransferase (HemL) từ α-ketoglutarate trong chu trình TCA thành 5-ALA và heme. Trong bài tổng quan này, chúng tôi mô tả những kết quả gần đây về sản xuất 5-ALA từ các gen và vi sinh vật khác nhau thông qua các phương pháp kỹ thuật di truyền và chuyển hóa. Sự điều chỉnh của các khung vi sinh vật khác nhau được tinh chỉnh bằng cách áp dụng sinh học tổng hợp và cuối cùng tăng cường sản xuất 5-ALA. Quá trình tinh chế, những thách thức và cơ hội của 5-ALA cho các ứng dụng công nghiệp cũng được tóm tắt.
Từ khóa
#5-aminolevulinic acid #sinh tổng hợp #kỹ thuật di truyền #chuyển hóa #quy trình sinh học #heme #ứng dụng công nghiệpTài liệu tham khảo
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