Tối ưu hóa chuyển hóa carbon trung tâm bằng hiệu ứng Warburg của tế bào ung thư con người cải thiện sinh tổng hợp triterpen trong nấm men
Tóm tắt
Tối ưu hóa chuyển hóa carbon trung tâm (CCM) là một chiến lược hấp dẫn và thách thức để cải thiện sinh tổng hợp các hóa chất có giá trị do sự điều tiết phức tạp của CCM trong nấm men. Trong nghiên cứu này, chúng tôi đã kích hoạt hiệu ứng Warburg tương tự của các tế bào ung thư trong các chủng nấm men bằng cách giới thiệu phức hợp yếu tố cảm ứng thiếu oxy-1 (HIF-1) của con người, phức hợp này điều chỉnh biểu hiện của nhiều enzyme tham gia vào CCM và định hướng lại dòng chuyển hóa từ quá trình glycosis sang chu trình axit tricarboxylic. Sự định hướng lại này đã thúc đẩy sản xuất squalene tăng 2,7 lần so với chủng đối chứng BY4741. Hơn nữa, phức hợp HIF-1 đã tăng cường sản xuất triterpenoid nội sinh ergosterol lên 1145,95 mg/L và triterpenoid ngoại sinh lupeol lên 236,35 mg/L trong nuôi cấy trong bình lắc, tăng 10,5 lần và 9,2 lần so với các chủng biến đổi mà không có sự tích hợp phức hợp HIF-1, tương ứng. Nghiên cứu này cung cấp một chiến lược mới để tối ưu hóa CCM bằng hiệu ứng Warburg trung gian HIF-1 của các tế bào ung thư nhằm cải thiện sinh tổng hợp triterpen trong nấm men.
Từ khóa
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