New Insights into the Modification of the Non-Core Metabolic Pathway of Steroids in Mycolicibacterium and the Application of Fermentation Biotechnology in C-19 Steroid Production

Abstract

Androsta-4-ene-3,17-dione (AD), androsta-1,4-diene-3,17-dione (ADD), and 9α-hydroxy-4-androstene-3,17-dione (9-OHAD), which belong to C-19 steroids, are critical steroid-based drug intermediates. The biotransformation of phytosterols into C-19 steroids by Mycolicibacterium cell factories is the core step in the synthesis of steroid-based drugs. The production performance of engineered mycolicibacterial strains has been effectively enhanced by sterol core metabolic modification. In recent years, research on the non-core metabolic pathway of steroids (NCMS) in mycolicibacterial strains has made significant progress. This review discusses the molecular mechanisms and metabolic modifications of NCMS for accelerating sterol uptake, regulating coenzyme I balance, promoting propionyl-CoA metabolism, reducing reactive oxygen species, and regulating energy metabolism. In addition, the recent applications of biotechnology in steroid intermediate production are summarized and compared, and the future development trend of NCMS research is discussed. This review provides powerful theoretical support for metabolic regulation in the biotransformation of phytosterols.

Recent progress of atmospheric and room‐temperature plasma as a new and promising mutagenesis technology

“…130 As biosynthesis has become increasingly popular, traditional methods usually have the problems of difficult process, complex by-products, low yield, and shortage of supply. In response, a number of efforts have been made, such as media optimization, 131 metabolic pathway modification, 132 and traditional breeding methods. 133 However, these methods and techniques are still limited and inefficient in obtaining the desired phenotype.…”

Green Manufacturing of Steroids via Mycolicbacteria: Current Status and Development Trends

“…In today's era, the field of chemistry has achieved remarkable feats. The advent of green synthesis methods has significantly alleviated environmental burdens while presenting novel methods for more efficient separation and purification of reaction products to achieve high reaction yields [24][25][26][27]. During the 1980s, the microbial transformation of sterols, which are by-products of mainly soy and paper production, gained rapid development and application, offering the advantages of reduced waste and increased productivity.…”