Aug 9, San Jose California – on the final morning of PlantSynBio19, researchers from academia and industry showcased the latest tools and technologies to manipulate plants for commercial production of bio-products

Synbio, Ag and Industry

Matt Mattozzi from Conagen provided an industry perspective on the production of food additives (for more see his interview  Plantae). Reliably sourcing natural flavors can be a big challenge as the result of batch effects, difficulties in extraction and global events such as droughts and flooding. Conagen aims to produce a reliable source of ingredients by moving some of the production process from plants into microbes that are amenable to fermentation processes.

Mattozzi talked about Conagen’s automated process optimization pipeline which includes the use of miniaturized “flowerplate” bioreactors to perform microliter volume trials before scaling up to commercial production volumes. Elaborating on the production of RebM BESTEVIA, one of thirty products made by Conagen, Matt described the process of bioprospecting, high-throughput cloning, automation and screening, to identify enzymes for the creation of new sweeteners with improved taste profiles.

Conagen’s integrated manufacturing chain. Source: Conagen Inc.

John Margolis, CSO at JoynBio – a joint venture between Bayer Crop Sciences and Gingko Bioworks, talked about the company’s efforts to produce biologicals (microbes) for Agriculture. The majority of corn grown in the US Midwest comes with a seed treatment that includes performance inducing microbes. JoynBio seeks to use genetic engineering to improve upon these treatments, focusing on crop nutrition, protection and quality, using highly characterized plant colonizing strains as chassis.

Margolis briefly touched upon active programs in nitrogen fixation and crop protection, where they perform bioprospecting for new enzymes which are then further improved by protein engineering in a genome foundry. By focusing on microbes rather than plants, Joyn is able to perform rapid engineering of strains with the potential to quickly reach the market.

Continuing on the theme of biologics, Karsten Temme, CEO at Pivot Bio, presented a vision for the sustainable fertilization of crops (his interview can be seen here). Leaching of fertilizer during torrential downpours can result in pollution of waterways and a loss in yield due to nutrient deprivation. Pivot Bio seeks to address this issue by reawakening the ability of root microbes to fix nitrogen in the presence of fertilizer and provide a consistent supply of nitrogen throughout the growing season.

Successful field trials suggest Pivot Bio’s microbes can produce anything from 25-35% of crop needs, reducing the amount of fertilizer needed and helping to reduce the carbon footprint of farming. 2019 is the first year of Pivot Bio PROVEN is being used across the Midwest and the company now plans to scale up production and tap new markets.

Source: Michigan Farm News

Cool tools from academia

Tautvydas Shuipys, a PhD student in the Folta Lab from the University of Florida, presented the characterization of a 6 amino acid peptide that inhibits plant responses to red-light. The production of herbicides with new modes has plateaued over the last decade and there has been an increase in the number of herbicide resistant crops. To address this the Folta lab has established the ‘random peptide project’ to identify new peptides that cold modulate plant growth. The mode of action of the new peptide is currently ongoing.

Hung Chiu-Yueh, a senior scientist at NC Central University, talked about glycoengineering, specifically a proof of principle project to produce recombinant “human-like” EPO. Many therapeutic and diagnostic proteins are glycoproteins but they are mostly produced in mammalian systems at high expense. To address this issue, Hung has been able to create significant quantities of glycosylated EPO by expressing six enzymes from humans in Tobacco to provide a foundation for further improvement.

Finally, Arjun Khakhar, a postdoc in Dan Voytas lab at the University of Minnesota, presented development of a system for rapid transcriptional reprograming in plants called VipariNama (from the Sanskrit “to change”). As mentioned elsewhere, one of the major bottlenecks in plant synthetic biology is phenotyping, which is typically slow as a result of the need for production of stable transgenic lines. To address this issue, Kharkhar started using ssRNA viruses to deliver synthetic transcription factors into plant tissues.

Building on his previous work to control plant development, Kharkar has created a system that uses Cas9 fused to transcriptional activators or repressors to modulate gene expression when gRNAs are delivered into plant tissues by VIN vectors. Continuously improving the system, he has incorporated movement enhancer sequences (FT protein from Arabidopsis) to try and overcome patchiness of expression, reduced suppression of constructs with the application of synthetic satellite viruses, switched to delivery of an ensemble of vectors to alleviate the need for generation of new stable lines to test each effector, and more.