Data underlying the study on Engineering class-B vitamin biosynthesis in Saccharomyces cerevisiae

<i>Saccharomyces cerevisiae</i> is bradytroph for class B vitamins, it means that yeast cells exhibit slower growth in the absence of an external source of these metabolites. Alleviating these nutritional requirements for optimal growth performance would represent a valuable phenotypic characteristic for industrial strains since this would result in cheaper processes that would also be less susceptible to contaminations. In the present study, suboptimal growth of <i>S. cerevisiae</i> in absence of either pantothenic acid, <i>para</i>-aminobenzoic acid (<i>p</i>ABA), pyridoxine, inositol and biotin were corrected by single or double gene overexpression of native <i>FMS1</i>, <i>ABZ1</i>/<i>ABZ2</i>, <i>SNZ1</i>/<i>SNO1</i>, <i>INO1</i> and the <i>Cyberlindnera fabianii BIO1</i>, respectively. Several strategies were attempted to improve growth of <i>S. cerevisiae</i> CEN.PK113-7D in absence of thiamine, revealing that overexpression of <i>THI4</i> and <i>THI4</i>/<i>THI5</i> was able to improve growth up to 83% of the maximum specific growth rate of the reference CEN.PK113-7D in medium including all vitamins. Although the initial aim of this study was to combine all identified mutations in a single strain, the engineered strain IMX2210 only harboured genes to correct biotin, <i>p</i>ABA, pantothenate and inositol bradotrophies. Firstly, this strain was fast-growing at a maximum specific growth rate of 0.28 ± 0.01 h^-1 in medium devoid of all vitamins. Secondly, this strain exhibited physiological variables in aerobic glucose limited chemostat cultures at a dilution rate of 0.1 h^-1 in absence of vitamins similar to that of the reference strain CEN.PK113-7D grown in the same conditions but in a fully supplemented complete medium. These physiological similarities were further emphasized by the limited differences observed in comparative transcriptome analysis from the chemostat culture grown cells that were essentially affecting genes of the class B vitamins biosynthetic pathways. This work paves the way towards construction of the first fast growing vitamin-independent <i>S. cerevisiae</i> strain.

酿酒酵母（Saccharomyces cerevisiae）属于B族维生素迟缓营养型（bradytroph），即当缺乏此类代谢物的外源供给时，酵母细胞的生长速率会显著减缓。解除此类营养依赖需求以实现最优生长性能，对于工业菌株而言是极具价值的表型特征，因为这可降低生产成本，同时降低污染易感风险。
本研究中，分别通过内源FMS1、ABZ1/ABZ2、SNZ1/SNO1、INO1以及费比恩类林德纳酵母（Cyberlindnera fabianii）BIO1的单基因或双基因过表达，修复了酿酒酵母在缺乏泛酸、对氨基苯甲酸（para-aminobenzoic acid，pABA）、吡哆醇、肌醇与生物素时的亚最优生长状态。
针对酿酒酵母CEN.PK113-7D在缺乏硫胺素时的生长缺陷，本研究尝试了多种优化策略，结果显示过表达THI4以及THI4/THI5可将其生长速率提升至参考菌株CEN.PK113-7D在完全维生素补充培养基中的最大比生长速率的83%。
尽管本研究最初目标是将所有已鉴定的突变整合至单一菌株，但最终构建的工程菌株IMX2210仅携带了修复生物素、pABA、泛酸与肌醇迟缓营养缺陷的相关基因。其一，该菌株在完全缺乏维生素的培养基中可实现快速生长，最大比生长速率达0.28 ± 0.01 h^-1；其二，在稀释率为0.1 h^-1的好氧葡萄糖限制恒化培养（无维生素添加）中，该菌株的生理指标与在完全补充培养基中相同条件下培养的参考菌株CEN.PK113-7D高度相似。
恒化培养细胞的比较转录组分析进一步印证了上述生理相似性，仅观察到有限的基因表达差异，且差异主要集中于B族维生素生物合成通路相关基因。本研究为首个快速生长且不依赖维生素的酿酒酵母菌株的构建铺平了道路。