Paclitaxel is a potent and widely used antitumor agent. Considerable worldwide research efforts have been carried out on different production alternatives. Since the description of the first paclitaxel-producing fungi, more than 15 years ago, microorganisms have been investigated as potential alternatives for an environmentally acceptable, relatively simple and inexpensive method to produce paclitaxel. However, in spite of significant research on paclitaxel-producing microorganisms, no commercial fermentation process has been implemented up to now. The aim of this study is to review the present status of research on paclitaxel-producing microorganisms and the ongoing efforts to develop heterologous paclitaxel biosynthesis, and analyze the perspectives of microbial fermentation for paclitaxel production.

BackgroundGrowth conditions that bring about stress on Phaffia rhodozyma cells encourage the synthesis of astaxanthin, an antioxidant carotenoid, which protects cells against oxidative damage. Using P. rhodozyma cultures performed with and without copper limitation, we examined the kinetics of astaxanthin synthesis along with the expression of asy, the key astaxanthin synthesis gene, as well as aox, which encodes an alternative oxidase protein.ResultsCopper deficiency had a detrimental effect on the rates of oxygen consumption and ethanol reassimilation at the diauxic shift. In contrast, copper deficiency prompted alcoholic fermentation under aerobic conditions and had a favorable effect on the astaxanthin content of cells, as well as on aox expression. Both cultures exhibited strong aox expression while consuming ethanol, but particularly when copper was absent.ConclusionWe show that the induction of either astaxanthin production, aox expression, or aerobic fermentation exemplifies the crucial role that redox imbalance plays in triggering any of these phenomena. Based on our own results and data from others, we propose a mechanism that rationalizes the central role played by changes of respiratory activity, which lead to redox imbalances, in triggering both the short-term antioxidant response as well as fermentation in yeasts and other cell types.

We evaluated the microbial diversity and metabolome profile of an uncommon hypersaline elastic microbial mat from Cuatro Ciénegas Basin (CCB) in the Chihuahuan Desert of Coahuila, México. We collected ten samples on a small scale transect (1.5-m) and described its microbial diversity through NGS-based ITS and 16S rDNA gene sequencing. A very low number of taxa comprised a considerable proportion of the mat and were shared across all sampling points, whereas the rare biosphere was more phylogenetically diverse (Faith’s Phylogenetic Diversity (FPD) index) and phylogenetically disperse (using a null model distribution of Phylogenetic Species Clustering (nmdPSC)) than the abundant (high read count) taxa for both analyzed libraries. We also found a distinctive metabolome profile for each sample and were able to tentatively annotate several classes of compounds with relevant biological properties.

Mangrove sediment ecosystems in the coastal areas of the Yucatan peninsula are unique environments, influenced by their karstic origin and connection with the world’s largest underground river. The microbial communities residing in these sediments are influenced by the presence of mangrove roots and the trading chemistry for communication between sediment bacteria and plant roots can be targeted for secondary metabolite research. To explore the secondary metabolite production potential of microbial community members in mangrove sediments at the “El Palmar” natural reserve in Sisal, Yucatan, a combined meta-omics approach was applied. The effects of a cultivation medium reported to select for actinomycetes within mangrove sediments’ microbial communities was also analyzed. The metabolome of the microbial communities was analyzed by high-resolution liquid chromatography-tandem mass spectrometry, and molecular networking analysis was used to investigate if known natural products and their variants were present. Metagenomic results suggest that the sediments from “El Palmar” harbor a stable bacterial community independently of their distance from mangrove tree roots. An unexpected decrease in the observed abundance of actinomycetes present in the communities occurred when an antibiotic-amended medium considered to be actinomycete-selective was applied for a 30-day period. However, the use of this antibiotic-amended medium also enhanced production of secondary metabolites within the microbial community present relative to the water control, suggesting the treatment selected for antibiotic-resistant bacteria capable of producing a higher number of secondary metabolites. Secondary metabolite mining of “El Palmar” microbial community metagenomes identified polyketide synthase and non-ribosomal peptide synthetases’ biosynthetic genes in all analyzed metagenomes. The presence of these genes correlated with the annotation of several secondary metabolites from the Global Natural Product Social Molecular Networking database. These results highlight the biotechnological potential of the microbial communities from “El Palmar”, and show the impact selective media had on the composition of communities of actinobacteria.

Phaffia rhodozyma is a basidiomycetous yeast that synthesizes astaxanthin (ASX), which is a powerful and highly valuable antioxidant carotenoid pigment. P. rhodozyma cells accrue ASX and gain an intense red-pink coloration when faced with stressful conditions such as nutrient limitations (e.g. nitrogen or copper), the presence of toxic substances (e.g. antimycin A), or are affected by mutations in the genes that are involved in nitrogen metabolism or respiration. Since cellular accrual of ASX occurs under a wide variety of conditions, this yeast represents a valuable model for studying the growth conditions that entail oxidative stress for yeast cells. Recently, we proposed that ASX synthesis can be largely induced by conditions that lead to reduction-oxidation (redox) imbalances, particularly the state of the NADH/NAD+ couple together with an oxidative environment. In this work, we review the multiple known conditions that elicit ASX synthesis expanding on the data that we formerly examined. When considered alongside the Mitchell's chemiosmotic hypothesis, the study served to rationalize the induction of ASX synthesis and other adaptive cellular processes under a much broader set of conditions. Our aim was to propose an underlying mechanism that explains how a broad range of divergent conditions converge to induce ASX synthesis in P. rhodozyma. The mechanism that links the induction of ASX synthesis with the occurrence of NADH/NAD+ imbalances may help in understanding how other organisms detect any of a broad array of stimuli or gene mutations, and then adaptively respond to activate numerous compensatory cellular processes.