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The inaugural Annual Symposium of Cold Spring Harbor Asia, entitled “Design and Synthesis of Biological Systems,” was organized by Daniel Gibson, Sang Yup Lee and Pamela Silver and held in November 2011. Speakers were invited to submit manuscripts in synthetic biology(SynBio) for peer review to Biotechnology Journal, resulting in the following 6 articles of this Focus issue.

A theme emerging from this meeting and the articles in this issue is that SynBio has advanced from first-generational successes and unexpected glitches to next-generational understanding and smarter engineering. The “Meeting Report: Cold Spring Harbor Asia – Design and Synthesis of Biological Systems” by Dokyun Na [1] summarizes the most important topics and speakers of the meeting.

Bacterial SynBio frequently runs into unpredicted, complicated problems. A broad review on “Contextualizing context for synthetic biology: Identifying causes of failure of synthetic biological systems” by Stefano Cardinale and Adam Arkin [2] classifies these problems, analyzes their causes and proposes methodologies for their control. SynBio has now moved beyond small-molecule synthesis to small-molecule drug discovery. But the journey was also important, demonstrating the power of SynBio to unintentionally force revision of hypotheses in basic molecular biology. Anthony Forster reviews these topics in “Synthetic biology challenges long-held hypotheses in translation, codon bias and transcription” [3], which was based on his talk at the conference. Uses of SynBio are no longer limited to microorganisms. The current status of plant SynBio applicable to design of functional synthetic components for detection of explosives and creation of hybrid synthetic-endogenous signaling pathways is reviewed by Kevin Morey et al. [4] entitled “Crosstalk between endogenous and synthetic components – synthetic signaling meets endogenous components”.

Synthetic biology has advanced from first-generational successes and unexpected glitches to next-generational understanding and smarter engineering.

Cloning GC-rich giant DNAs is a daunting task. In this issue, Naoto Ohtani et al. [5] present their study “Serial assembly of Thermus megaplasmid DNA in the genome of Bacillus subtilis 16S: A BAC-based domino method applied to DNA with a high GC content”, which creates a suitable methodology for assembly of GC-rich DNAs, while the upper size limit of the DNA inserts is examined. As metabolic engineering is becoming an essential discipline to generate microbial strains for the efficient production of chemicals, fuels and materials, it is important to develop methods for introducing new functions into a host strain. The Research Article “Engineering of self-sustaining systems: Substituting the yeast glucose transporter plus hexokinase for the Lactococcuslactis phosphotransferase system in a L. lactis network in silico” by Malgorzata Adamczyk and Hans Westerhoff [6] establishes in silico the feasibility of engineering metabolism without changing metabolite concentrations.

We are grateful for the dedicated editorial assistance of Jing Zhu (Wiley, Shanghai, China) and Uta Göbel (Wiley, Weinheim, Germany).

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Prof. Anthony C. Forster, Uppsala University

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Prof. Sang Yup Lee, Editor-in-Chief, Biotechnology Journal, Korea Advanced Institute of Science and Technology (KAIST)

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