Yeast as a promising heterologous host for steroid bioproduction
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METABOLIC ENGINEERING AND SYNTHETIC BIOLOGY - MINI REVIEW
Yeast as a promising heterologous host for steroid bioproduction Shanhui Xu1 · Yanran Li1 Received: 30 April 2020 / Accepted: 6 July 2020 © Society for Industrial Microbiology and Biotechnology 2020
Abstract With the rapid development of synthetic biology and metabolic engineering technologies, yeast has been generally considered as promising hosts for the bioproduction of secondary metabolites. Sterols are essential components of cell membrane, and are the precursors for the biosynthesis of steroid hormones, signaling molecules, and defense molecules in the higher eukaryotes, which are of pharmaceutical and agricultural significance. In this mini-review, we summarize the recent engineering efforts of using yeast to synthesize various steroids, and discuss the structural diversity that the current steroidproducing yeast can achieve, the challenge and the potential of using yeast as the bioproduction platform of various steroids from higher eukaryotes. Keywords Yeast · Steroids · Biotransformation · De novo synthesis · Metabolic engineering
Introduction Sterols are essential membrane components that regulate membrane fluidity and permeability in eukaryotic organisms [1]. Animals generally synthesize cholesterol, fungi produce ergosterol, and plants utilize an array of sterols with β-sitosterol and campesterol as the most common ones [1]. Despite the essential roles in membrane modulation, sterols also exhibit important bioactivities. For example, due to the structural similarity to cholesterol, phytosterols can reduce cholesterol absorption in digestive system and reduce the risk of heart disease [2, 3]. In higher eukaryotes, sterols are also precursors to a wide array of specialized metabolites with broad structural diversity and biological activities. In insects, cholesterol is converted into insect steroid hormones, such as ecdysteroids that can be potentially utilized as anabolic steroids [4]. In human, cholesterol is the precursor to an array of steroid hormones such as progesterone and vitamin D [5, 6]. In plants, campesterol is the main precursor of the ubiquitous phytohormone brassinosteroids [7]; cholesterol, although exhibits very low abundance in plants, is the precursor to a broad spectrum of phytochemicals, such * Yanran Li [email protected] 1
Department of Chemical and Environmental Engineering, 900 University Avenue, Bourns Hall, Suite A220, Riverside, CA 92521, USA
as the medicinally important steroidal alkaloids and steroidal saponins [8]. Intriguingly, some phytosteroids exhibit promising antiviral activities via different mechanisms, which make them intriguing lead structures for novel antiviral drug discovery and development [9–12]. Plants also produce ecdysteroid analogs, phytoecdysteroids, as natural defense mechanism against phytophagous insects [4]. Moreover, steroids are an important pharmaceutical medication, with the global steroid market projected to reach $17 billion in 2025 [13]. Steroid drugs generally fall into tw
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