Khám Phá Sản Phẩm Tự Nhiên: Quá Khứ, Hiện Tại và Tương Lai
Tóm tắt
Các vi sinh vật đã cung cấp nguồn tài nguyên phong phú của các sản phẩm tự nhiên, từ đó phát triển thành các sản phẩm thương mại phục vụ cho y học, sức khỏe động vật và bảo vệ cây trồng. Trong những năm đầu của việc phát hiện sản phẩm tự nhiên từ vi sinh vật (Thời Đại Vàng), các kháng sinh mới được tìm thấy một cách tương đối dễ dàng thông qua các phương pháp lên men có sản lượng thấp và sàng lọc toàn bộ tế bào. Sau đó, các phương pháp di truyền phân tử và hóa học dược phẩm đã được áp dụng để sửa đổi và cải thiện hoạt động của các khung hóa học quan trọng, và các phương pháp sàng lọc tinh vi hơn đã được hướng đến các trạng thái bệnh lý mục tiêu. Vào những năm 1990, ngành công nghiệp dược phẩm đã chuyển sang việc sàng lọc công suất cao các thư viện hóa chất tổng hợp nhằm vào nhiều mục tiêu điều trị tiềm năng, bao gồm cả các mục tiêu mới được xác định từ dự án giải trình tự gen người, phần lớn là để loại trừ các sản phẩm tự nhiên, và tỷ lệ phát hiện đã giảm mạnh. Tuy nhiên, các sản phẩm tự nhiên vẫn tiếp tục cung cấp các khung hóa học chính cho việc phát triển thuốc. Trong thiên niên kỷ hiện tại, thông qua giải trình tự gen, người ta phát hiện rằng các vi sinh vật có bộ gen lớn có khả năng sản xuất khoảng gấp mười lần số lượng chuyển hóa thứ cấp so với những gì đã được công nhận trước đó. Thực tế, các actinobacteria tài năng nhất có khả năng sản xuất khoảng 30–50 chuyển hóa thứ cấp. Với sự giảm mạnh trong chi phí giải trình tự gen, hiện nay có thể tiến hành giải trình tự hàng nghìn bộ gen actinobacteria để xác định "vật chất tối sinh học" như là nguồn cho việc phát hiện các chuyển hóa thứ cấp mới và độc đáo. Những tiến bộ trong sinh tin học, phổ khối, proteomics, transcriptomics, metabolomics và biểu hiện gen đang thúc đẩy lĩnh vực mới của việc khai thác bộ gen vi sinh vật nhằm ứng dụng trong việc phát hiện và phát triển sản phẩm tự nhiên.
Từ khóa
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