Vitamin requirements and biosynthesis in Saccharomyces cerevisiae

Abstract

Chemically defined media for yeast cultivation (CDMY) were developed to support fast growth, experimental reproducibility, and quantitative analysis of growth rates and biomass yields. In addition to mineral salts and a carbon substrate, popular CDMYs contain seven to nine B‐group vitamins, which are either enzyme cofactors or precursors for their synthesis. Despite the widespread use of CDMY in fundamental and applied yeast research, the relation of their design and composition to the actual vitamin requirements of yeasts has not been subjected to critical review since their first development in the 1940s. Vitamins are formally defined as essential organic molecules that cannot be synthesized by an organism. In yeast physiology, use of the term “vitamin” is primarily based on essentiality for humans, but the genome of the Saccharomyces cerevisiae reference strain S288C harbours most of the structural genes required for synthesis of the vitamins included in popular CDMY. Here, we review the biochemistry and genetics of the biosynthesis of these compounds by S. cerevisiae and, based on a comparative genomics analysis, assess the diversity within the Saccharomyces genus with respect to vitamin prototrophy.

Adaptive laboratory evolution and reverse engineering of single-vitamin prototrophies inSaccharomyces cerevisiae

“…The observation that Saccharomyces yeasts can de novo synthesize some or all of the ‘B-vitamins’ included in CDMY is consistent with the presence of structural genes encoding the enzymes required for their biosynthesis (Fig. 1, (5)). However, as illustrated by recent studies on biotin requirements of S. cerevisiae CEN.PK113-7D (5, 9), a full complement of biosynthetic genes is not necessarily sufficient for fast growth in the absence of an individual vitamin.…”

“…Based on their water solubility and roles in the human diet, these compounds are all referred to as B-vitamins, but their chemical structures and cellular functions are very different (4). Taking into account their roles in metabolism, they can be divided into three groups i) enzyme co-factors (biotin, pyridoxine, thiamine), ii) precursors for co-factor biosynthesis (nicotinic acid, p ABA, pantothenic acid) and iii) inositol, which is a precursor for phosphoinositol and glycosylphosphoinositol anchor proteins (5).…”

“…Previous studies demonstrated that growth of Saccharomyces species does not strictly depend on addition of all of these B-vitamins, but that omission of individual compounds from CDMY typically results in reduced specific growth rates (6–8). These observations imply that the term ‘vitamin’, which implies a strict nutritional requirement, is in many cases formally incorrect when referring to the role of these compounds in S. cerevisiae metabolism (5). In view of its widespread use in yeast physiology, we will nevertheless use it in this paper.…”

“…1, (5)). However, as illustrated by recent studies on biotin requirements of S. cerevisiae CEN.PK113-7D (5, 9), a full complement of biosynthetic genes is not necessarily sufficient for fast growth in the absence of an individual vitamin. In the absence of biotin, this grew extremely slowly (µ < 0.01 h -1 ), but fast biotin-independent growth could be obtained through prolonged adaptive laboratory evolution (ALE) in a biotin-free CDMY.…”

“… Schematic representation of the de novo biosynthetic pathways for the B-vitamins biotin (A), nicotinic acid (B), myo-inositol (C), pantothenate (D), pABA (E), pyridoxine and thiamine (F) in S. cerevisiae (5). Vitamins that are usually added to the chemical defined media for cultivation of yeasts are shown in blue.…”